Diffuse Large B-cell Lymphoma
Conditions
Keywords
Relapsed DLBCL, Refractory DLBCL, adult DLBCL, Lymphoma, Non-Hodgkin Lymphoma, Lymphatic diseases, Lymphoproliferative disorders, bispecific antibody, anti-CD19, Immunotherapeutic treatment, Immunoproliferative disorders
Brief summary
The purpose of this study is to confirm whether the bispecific T-cell engager blinatumomab is effective and safe in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Detailed description
DLBCL is an aggressive malignant disease which evolves from B-cells and affects mainly the lymphatic tissue. Due to its aggressive nature the disease is characterized by a fast course which is lethal without therapy. Potentially curative therapy options are available even at advanced stages. Standard-first line leads to a high initial response rate (85-90%) and an approximate cure rate of 50% of patients. Patients refractory to or with early relapse after this treatment (10-15%) have a very poor prognosis. Blinatumomab is a bispecific single-chain antibody derivative against CD19 and CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells. This study consisted of a screening period, treatment period, and a follow-up efficacy and survival period. The core study comprises the treatment period to the 30 days after the last infusion. The first cycle consisted of a continuous intravenous (CIV) infusion over 8 weeks. Participants who achieved a Complete Response (CR) or Partial Response (PR) or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. After the last treatment cycle, efficacy and survival follow-up visits occurred for up to 24 months from treatment start. Participants who relapsed during the follow-up period may have received an additional 8 weeks of treatment. Two dose regimens were assessed in this study. Stage 1 comprised 2 dose cohorts. In Cohort 1, the first 6 participants were to receive blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. In Cohort 2, the next 6 participants enrolled were to receive a constant dose of 112 µg/day blinatumomab. Before the initiation of stage 2, a pre-planned data monitoring committee (DMC) meeting was held to assess the safety profile of Cohort 1 and Cohort 2. The dosing regimen with the more favorable benefit-risk profile was to be selected for Cohort 3.
Interventions
DRUGBlinatumomab
Administered by continuous intravenous infusion over 8 weeks in the first cycle and 4 weeks in the second cycle.
Sponsors
Amgen Research (Munich) GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with Diffuse Large B-Cell Lymphoma (DLBCL) who are refractory to first or later treatment or have a first relapse or later relapse not eligible for autologous hematopoietic stem cell transplant (HSCT) or relapsed post- autologous-HSCT * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Age ≥ 18 years * Life expectancy of ≥ 12 weeks * Cerebrospinal fluid (CSF) free of infiltration by DLBCL
Exclusion criteria
* History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis * Current infiltration of CSF by DLBCL * History of autoimmune disease with potential CNS involvement or current autoimmune disease * Autologous HSCT within six weeks prior to start of blinatumomab treatment * Prior allogeneic HSCT * Cancer chemotherapy within two weeks prior to start of blinatumomab treatment * Radiotherapy within four weeks prior to start of blinatumomab treatment * Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treatment * Any investigational anti-lymphoma product within four weeks prior to start of blinatumomab treatment * Treatment with any other investigational product after signature of informed consent * Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation * Abnormal laboratory values indicative of inadequate renal or liver function * History of malignancy other than non-Hodgkin's lymphoma (NHL) within five years prior to start of blinatumomab treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix * Active uncontrolled infection, any other concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator * Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus * Pregnant or nursing women * Previous treatment with blinatumomab * Presence of human anti-murine antibodies (HAMA) at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response Rate During Treatment Cycle 1 | During the first 8 weeks | Overall response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all evidence of disease and partial response is defined as regression of measureable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Partial Response | During the first 8 weeks | Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (\<50% decrease in size of masses) of measureable disease and no new sites. |
| Duration of Objective Response | From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months. | The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. |
| Duration of Complete Response | From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months. | The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. |
| Duration of Partial Response | From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months. | The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. |
| Progression-free Survival (PFS) | From first infusion of blinatumomab until the end of study; median time on follow-up for PFS was 27.0 months. | The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment. |
| Overall Survival (OS) | From the first infusion of blinatumomab until the end of study; median time on follow-up for overall survival was 26.6 months. | The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed. |
| Number of Participants With Adverse Events | From the first dose of blinatumomab until up to 30 days after the last dose or until the data cut-off date of 10 July 2014, whichever occurred first; the overall median duration of treatment exposure was 46.8 days. | Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. An adverse event or suspected adverse drug reaction was considered serious if it resulted in one of the following outcomes: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions; * Was a congenital anomaly or birth defect; * Was a medically important condition. The Investigator used medical judgment to determine whether there was a causal relationship (ie, related \[reasonably possible\] or unrelated \[not reasonably possible\]) between an adverse event and blinatumomab. |
| Blinatumomab Steady State Serum Concentration | Cycle 1: predose; Day 3 and Day 8 (Css for 9 ug/day); Day 15 (Css for 28 ug/day); and Day 29, Day 43 and Day 57 (Css for 112 ug/day) | Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day. |
| Leukocyte Counts | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Leukocyte (white blood cells) counts were analyzed by differential blood count analysis. |
| Lymphocyte Counts | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Lymphocyte counts were analyzed by differential blood count analysis. |
| Monocyte Counts | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | — |
| Granulocyte Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | — |
| CD19+ B-Cell Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD19+ B-cell counts were analyzed by flow cytometry. |
| CD19+ B-Cells as a Percentage of All Lymphocytes | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD19+ B-cell counts were analyzed by flow cytometry. |
| CD3+ T-Cell Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD3+ T-cell counts were analyzed by flow cytometry. |
| CD3+ T-Cells as a Percentage of All Lymphocytes | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD3+ T-cell counts were analyzed by flow cytometry. |
| CD4+ T-Cell Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD4+ T-cell counts were analyzed by flow cytometry. |
| CD4+ T-Cells as a Percentage of All Lymphocytes | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD4+ T-cell counts were analyzed by flow cytometry. |
| Percentage of Participants With a Best Overall Response of Complete Response | During the first 8 weeks | Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Complete response is defined as the disappearance of all evidence of disease. |
| CD8+ T-Cells as a Percentage of All Lymphocytes | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD8+ T-cell counts were analyzed by flow cytometry. |
| CD19+ B-Cell to CD3+ T-Cell Ratio | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry. |
| CD4+ T-Cell to CD8+ T-Cell Ratio | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry. |
| CD4+ Naive T Cell Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD4+ Central Memory T-Cell (TCM) Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry. |
| CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry. |
| CD4+ Effector Memory T-Cell (TEM) Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD8+ Naive T-Cell Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD8+ TCM Cell Counts | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry. |
| CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry. |
| CD8+ Effector Memory T-Cell (TEM) Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry. |
| CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry. |
| CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry. |
| CD8+ T-Cell Count | Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment | CD8+ T-cell counts were analyzed by flow cytometry. |
Countries
Germany
Participant flow
Recruitment details
Adults with a diagnosis of diffuse large B-cell lymphoma (DLBCL) which was refractory to first or subsequent treatment or who had a first or later relapse and were not eligible for autologous hematopoietic stem cell transplant (HSCT), or relapsed after autologous HSCT were eligible to enrol. The primary analysis cut-off date was 10 July 2014.
Pre-assignment details
The study was conducted sequentially in 2 stages and 3 cohorts: In Stage 1, Cohort 1 received an escalating dose of 9/28/112 µg/day blinatumomab and Cohort 2 received a constant dose of 112 µg/day for 8 weeks. In Stage 2, the Cohort 3 dose regimen was determined from the outcome of Cohorts 1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Blinatumomab 9/28/112 µg/d Participants received blinatumomab administered via a continuous intravenous infusion (CIV) 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved a complete response (CR) or partial response (PR), or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. | 9 |
| Cohort 2: Blinatumomab 112 µg/d Participants received blinatumomab administered CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved a CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. | 2 |
| Cohort 3: Blinatumomab 9/28/112 µg/d Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. | 14 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 6 | 1 | 12 |
Baseline characteristics
| Characteristic | Cohort 1: Blinatumomab 9/28/112 µg/d | Cohort 2: Blinatumomab 112 µg/d | Cohort 3: Blinatumomab 9/28/112 µg/d | Total |
|---|---|---|---|---|
| Age, Continuous | 71.7 years STANDARD_DEVIATION 7.8 | 64.5 years STANDARD_DEVIATION 13.4 | 57.1 years STANDARD_DEVIATION 13.6 | 62.9 years STANDARD_DEVIATION 13.3 |
| Gender Female | 7 Participants | 0 Participants | 4 Participants | 11 Participants |
| Gender Male | 2 Participants | 2 Participants | 10 Participants | 14 Participants |
| Number of Previous Autologous Hematopoietic Stem Cell Transplants (HSCT) ≥ 1 | 2 participants | 1 participants | 4 participants | 7 participants |
| Number of Previous Autologous Hematopoietic Stem Cell Transplants (HSCT) None | 7 participants | 1 participants | 10 participants | 18 participants |
| Race/Ethnicity, Customized White | 9 participants | 2 participants | 14 participants | 25 participants |
| Relapsed/refractory Status to Last Prior Treatment Refractory | 5 participants | 1 participants | 10 participants | 16 participants |
| Relapsed/refractory Status to Last Prior Treatment Relapsed | 4 participants | 1 participants | 4 participants | 9 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 2 / 2 | 14 / 14 | 23 / 23 | 25 / 25 |
| serious Total, serious adverse events | 9 / 9 | 2 / 2 | 12 / 14 | 21 / 23 | 23 / 25 |
Outcome results
Primary
Overall Objective Response Rate During Treatment Cycle 1
Overall response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all evidence of disease and partial response is defined as regression of measureable disease and no new sites.
Time frame: During the first 8 weeks
Population: Efficacy Set includes all participants who completed at least 7 days of infusion on the highest intended dose level.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Overall Objective Response Rate During Treatment Cycle 1 | 57.1 percentage of participants |
| Cohort 2: Blinatumomab 112 μg/d | Overall Objective Response Rate During Treatment Cycle 1 | 100.0 percentage of participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Overall Objective Response Rate During Treatment Cycle 1 | 30.8 percentage of participants |
Secondary
Blinatumomab Steady State Serum Concentration
Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day.
Time frame: Cycle 1: predose; Day 3 and Day 8 (Css for 9 ug/day); Day 15 (Css for 28 ug/day); and Day 29, Day 43 and Day 57 (Css for 112 ug/day)
Population: Pharmacokinetic (PK) data set (all participants who received any infusion of blinatumomab and had at least one PK sample collected).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Blinatumomab Steady State Serum Concentration | 277 pg/mL | Standard Deviation 210 |
| Cohort 2: Blinatumomab 112 μg/d | Blinatumomab Steady State Serum Concentration | 565 pg/mL | Standard Deviation 208 |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Blinatumomab Steady State Serum Concentration | 2800 pg/mL | Standard Deviation 1150 |
Secondary
CD19+ B-Cell Count
CD19+ B-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | Screening (N = 25) | 0.026 1000 cells/µL | Standard Deviation 0.072 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | Day 1 Prior (N = 24) | 0.029 1000 cells/µL | Standard Deviation 0.085 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | Day 8 (N = 21) | 0.001 1000 cells/µL | Standard Deviation 0.002 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | Day 15 (N = 16) | 0.000 1000 cells/µL | Standard Deviation 0.001 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | Day 29 (N = 11) | 0.000 1000 cells/µL | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | Day 43 (N = 8) | 0.000 1000 cells/µL | Standard Deviation 0.001 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | End of Infusion (N = 9) | 0.001 1000 cells/µL | Standard Deviation 0.001 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | End of Core Study (N = 6) | 0.001 1000 cells/µL | Standard Deviation 0.002 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 3-Month Follow-up (N = 5) | 0.025 1000 cells/µL | Standard Deviation 0.026 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 6-Month Follow-up (N = 6) | 0.029 1000 cells/µL | Standard Deviation 0.043 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 9-Month Follow-up (N = 4) | 0.054 1000 cells/µL | Standard Deviation 0.066 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 12-Month Follow-up (N = 4) | 0.082 1000 cells/µL | Standard Deviation 0.113 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 15-Month Follow-up (N = 3) | 0.094 1000 cells/µL | Standard Deviation 0.118 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 18-Month Follow-up (N = 3) | 0.071 1000 cells/µL | Standard Deviation 0.075 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 21-Month Follow-up (N = 21) | 0.131 1000 cells/µL | Standard Deviation 0.17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell Count | 24-Month Follow-up (N = 3) | 0.108 1000 cells/µL | Standard Deviation 0.12 |
Secondary
CD19+ B-Cells as a Percentage of All Lymphocytes
CD19+ B-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | Screening (N = 25) | 2 percentage of lymphocytes | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | Day 1 Prior (N = 24) | 4 percentage of lymphocytes | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | Day 8 (N = 21) | 0 percentage of lymphocytes | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | Day 15 (N = 16) | 0 percentage of lymphocytes | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | Day 29 (N = 11) | 0 percentage of lymphocytes | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | Day 43 (N = 8) | 0 percentage of lymphocytes | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | End of Infusion (N = 9) | 0 percentage of lymphocytes | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | End of Core Study (N = 6) | 0 percentage of lymphocytes | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 3-Month Follow-up (N = 5) | 2 percentage of lymphocytes | Standard Deviation 2 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 6-Month Follow-up (N = 6) | 2 percentage of lymphocytes | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 9-Month Follow-up (N = 4) | 5 percentage of lymphocytes | Standard Deviation 5 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 12-Month Follow-up (N = 4) | 7 percentage of lymphocytes | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 15-Month Follow-up (N = 3) | 7 percentage of lymphocytes | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 18-Month Follow-up (N = 3) | 11 percentage of lymphocytes | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 21-Month Follow-up (N = 21) | 8 percentage of lymphocytes | Standard Deviation 8 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cells as a Percentage of All Lymphocytes | 24-Month Follow-up (N = 3) | 12 percentage of lymphocytes | Standard Deviation 7 |
Secondary
CD19+ B-Cell to CD3+ T-Cell Ratio
CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | Screening (N = 25) | 0.04 ratio | Standard Deviation 0.15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | Day 1 Prior (N = 24) | 0.07 ratio | Standard Deviation 0.24 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | Day 8 (N = 21) | 0.00 ratio | Standard Deviation 0.01 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | Day 15 (N = 16) | 0.00 ratio | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | Day 29 (N = 11) | 0.00 ratio | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | Day 43 (N = 8) | 0.00 ratio | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | End of Infusion (N = 9) | 0.00 ratio | Standard Deviation 0.01 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | End of Core Study (N = 6) | 0.00 ratio | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 3-Month Follow-up (N = 5) | 0.03 ratio | Standard Deviation 0.03 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 6-Month Follow-up (N = 6) | 0.04 ratio | Standard Deviation 0.05 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 9-Month Follow-up (N = 4) | 0.08 ratio | Standard Deviation 0.08 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 12-Month Follow-up (N = 4) | 0.12 ratio | Standard Deviation 0.15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 15-Month Follow-up (N = 3) | 0.13 ratio | Standard Deviation 0.13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 18-Month Follow-up (N = 3) | 0.25 ratio | Standard Deviation 0.3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 21-Month Follow-up (N = 21) | 0.17 ratio | Standard Deviation 0.2 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD19+ B-Cell to CD3+ T-Cell Ratio | 24-Month Follow-up (N = 3) | 0.19 ratio | Standard Deviation 0.13 |
Secondary
CD3+ T-Cell Count
CD3+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | Screening (N = 25) | 0.578 1000 cells/µL | Standard Deviation 0.355 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | Day 1 Prior (N = 24) | 0.349 1000 cells/µL | Standard Deviation 0.233 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | Day 8 (N = 21) | 0.282 1000 cells/µL | Standard Deviation 0.194 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | Day 15 (N = 16) | 0.199 1000 cells/µL | Standard Deviation 0.159 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | Day 29 (N = 11) | 0.348 1000 cells/µL | Standard Deviation 0.231 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | Day 43 (N = 8) | 0.613 1000 cells/µL | Standard Deviation 0.426 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | End of Infusion (N = 9) | 0.543 1000 cells/µL | Standard Deviation 0.421 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | End of Core Study (N = 6) | 0.825 1000 cells/µL | Standard Deviation 0.431 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 3-Month Follow-up (N = 5) | 0.773 1000 cells/µL | Standard Deviation 0.443 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 6-Month Follow-up (N = 6) | 0.782 1000 cells/µL | Standard Deviation 0.345 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 9-Month Follow-up (N = 4) | 0.671 1000 cells/µL | Standard Deviation 0.184 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 12-Month Follow-up (N = 4) | 0.703 1000 cells/µL | Standard Deviation 0.203 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 15-Month Follow-up (N = 3) | 0.594 1000 cells/µL | Standard Deviation 0.227 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 18-Month Follow-up (N = 3) | 0.298 1000 cells/µL | Standard Deviation 0.049 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 21-Month Follow-up (N = 21) | 0.623 1000 cells/µL | Standard Deviation 0.266 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cell Count | 24-Month Follow-up (N = 3) | 0.456 1000 cells/µL | Standard Deviation 0.257 |
Secondary
CD3+ T-Cells as a Percentage of All Lymphocytes
CD3+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | Screening (N = 25) | 72 percentage of lymphocytes | Standard Deviation 14 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | Day 1 Prior (N = 24) | 68 percentage of lymphocytes | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | Day 8 (N = 21) | 70 percentage of lymphocytes | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | Day 15 (N = 16) | 67 percentage of lymphocytes | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | Day 29 (N = 11) | 73 percentage of lymphocytes | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | Day 43 (N = 8) | 71 percentage of lymphocytes | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | End of Infusion (N = 9) | 66 percentage of lymphocytes | Standard Deviation 14 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | End of Core Study (N = 6) | 76 percentage of lymphocytes | Standard Deviation 16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 3-Month Follow-up (N = 5) | 73 percentage of lymphocytes | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 6-Month Follow-up (N = 6) | 66 percentage of lymphocytes | Standard Deviation 21 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 9-Month Follow-up (N = 4) | 66 percentage of lymphocytes | Standard Deviation 6 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 12-Month Follow-up (N = 4) | 65 percentage of lymphocytes | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 15-Month Follow-up (N = 3) | 61 percentage of lymphocytes | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 18-Month Follow-up (N = 3) | 57 percentage of lymphocytes | Standard Deviation 20 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 21-Month Follow-up (N = 21) | 58 percentage of lymphocytes | Standard Deviation 16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD3+ T-Cells as a Percentage of All Lymphocytes | 24-Month Follow-up (N = 3) | 63 percentage of lymphocytes | Standard Deviation 8 |
Secondary
CD4+ Central Memory T-Cell (TCM) Count
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | Screening (N = 25) | 0.048 1000 cells/µL | Standard Deviation 0.053 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | Day 1 Prior (N = 24) | 0.029 1000 cells/µL | Standard Deviation 0.034 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | Day 8 (N = 21) | 0.027 1000 cells/µL | Standard Deviation 0.042 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | Day 15 (N = 16) | 0.014 1000 cells/µL | Standard Deviation 0.025 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | Day 29 (N = 11) | 0.032 1000 cells/µL | Standard Deviation 0.065 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | Day 43 (N = 8) | 0.032 1000 cells/µL | Standard Deviation 0.035 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | End of Infusion (N = 9) | 0.049 1000 cells/µL | Standard Deviation 0.103 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | End of Core Study (N = 6) | 0.062 1000 cells/µL | Standard Deviation 0.075 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 3-Month Follow-up (N = 5) | 0.019 1000 cells/µL | Standard Deviation 0.009 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 6-Month Follow-up (N = 6) | 0.027 1000 cells/µL | Standard Deviation 0.02 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 9-Month Follow-up (N = 4) | 0.043 1000 cells/µL | Standard Deviation 0.056 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 12-Month Follow-up (N = 4) | 0.065 1000 cells/µL | Standard Deviation 0.073 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 15-Month Follow-up (N = 3) | 0.039 1000 cells/µL | Standard Deviation 0.02 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 18-Month Follow-up (N = 3) | 0.033 1000 cells/µL | Standard Deviation 0.031 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 21-Month Follow-up (N = 21) | 0.056 1000 cells/µL | Standard Deviation 0.054 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Central Memory T-Cell (TCM) Count | 24-Month Follow-up (N = 3) | 0.021 1000 cells/µL | Standard Deviation 0.01 |
Secondary
CD4+ Effector Memory T-Cell (TEM) Count
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | Screening (N = 25) | 0.161 1000 cells/µL | Standard Deviation 0.089 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | Day 1 Prior (N = 24) | 0.099 1000 cells/µL | Standard Deviation 0.096 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | Day 8 (N = 21) | 0.083 1000 cells/µL | Standard Deviation 0.076 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | Day 15 (N = 16) | 0.051 1000 cells/µL | Standard Deviation 0.044 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | Day 29 (N = 11) | 0.097 1000 cells/µL | Standard Deviation 0.059 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | Day 43 (N = 8) | 0.169 1000 cells/µL | Standard Deviation 0.117 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | End of Infusion (N = 9) | 0.140 1000 cells/µL | Standard Deviation 0.091 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | End of Core Study (N = 6) | 0.220 1000 cells/µL | Standard Deviation 0.142 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 3-Month Follow-up (N = 5) | 0.279 1000 cells/µL | Standard Deviation 0.153 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 6-Month Follow-up (N = 6) | 0.267 1000 cells/µL | Standard Deviation 0.158 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 9-Month Follow-up (N = 4) | 0.191 1000 cells/µL | Standard Deviation 0.037 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 12-Month Follow-up (N = 4) | 0.226 1000 cells/µL | Standard Deviation 0.1 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 15-Month Follow-up (N = 3) | 0.199 1000 cells/µL | Standard Deviation 0.087 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 18-Month Follow-up (N = 3) | 0.106 1000 cells/µL | Standard Deviation 0.066 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 21-Month Follow-up (N = 21) | 0.181 1000 cells/µL | Standard Deviation 0.107 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Effector Memory T-Cell (TEM) Count | 24-Month Follow-up (N = 3) | 0.175 1000 cells/µL | Standard Deviation 0.133 |
Secondary
CD4+ Naive T Cell Count
CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | Screening (N = 25) | 0.028 1000 cells/µL | Standard Deviation 0.056 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | Day 1 Prior (N = 24) | 0.013 1000 cells/µL | Standard Deviation 0.022 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | Day 8 (N = 21) | 0.014 1000 cells/µL | Standard Deviation 0.033 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | Day 15 (N = 16) | 0.012 1000 cells/µL | Standard Deviation 0.024 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | Day 29 (N = 11) | 0.032 1000 cells/µL | Standard Deviation 0.071 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | Day 43 (N = 8) | 0.036 1000 cells/µL | Standard Deviation 0.06 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | End of Infusion (N = 9) | 0.037 1000 cells/µL | Standard Deviation 0.088 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | End of Core Study (N = 6) | 0.050 1000 cells/µL | Standard Deviation 0.083 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 3-Month Follow-up (N = 5) | 0.015 1000 cells/µL | Standard Deviation 0.019 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 6-Month Follow-up (N = 6) | 0.023 1000 cells/µL | Standard Deviation 0.044 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 9-Month Follow-up (N = 4) | 0.053 1000 cells/µL | Standard Deviation 0.09 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 12-Month Follow-up (N = 4) | 0.053 1000 cells/µL | Standard Deviation 0.084 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 15-Month Follow-up (N = 3) | 0.044 1000 cells/µL | Standard Deviation 0.059 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 18-Month Follow-up (N = 3) | 0.035 1000 cells/µL | Standard Deviation 0.041 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 21-Month Follow-up (N = 21) | 0.098 1000 cells/µL | Standard Deviation 0.103 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cell Count | 24-Month Follow-up (N = 3) | 0.016 1000 cells/µL | Standard Deviation 0.013 |
Secondary
CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells
CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Screening (N = 25) | 8 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Day 1 Prior (N = 24) | 7 percentage of CD4+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Day 8 (N = 21) | 7 percentage of CD4+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Day 15 (N = 16) | 10 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Day 29 (N = 11) | 9 percentage of CD4+ T-cells | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | Day 43 (N = 8) | 10 percentage of CD4+ T-cells | Standard Deviation 10 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | End of Infusion (N = 9) | 8 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | End of Core Study (N = 6) | 9 percentage of CD4+ T-cells | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 3-Month Follow-up (N = 5) | 4 percentage of CD4+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 6-Month Follow-up (N = 6) | 4 percentage of CD4+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 9-Month Follow-up (N = 4) | 11 percentage of CD4+ T-cells | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 12-Month Follow-up (N = 4) | 12 percentage of CD4+ T-cells | Standard Deviation 14 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 15-Month Follow-up (N = 3) | 10 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 18-Month Follow-up (N = 3) | 19 percentage of CD4+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 21-Month Follow-up (N = 21) | 23 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells | 24-Month Follow-up (N = 3) | 8 percentage of CD4+ T-cells | Standard Deviation 10 |
Secondary
CD4+ T-Cell Count
CD4+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | Day 8 (N = 21) | 0.131 1000 cells/µL | Standard Deviation 0.128 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | Day 15 (N = 16) | 0.085 1000 cells/µL | Standard Deviation 0.084 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | Day 29 (N = 11) | 0.170 1000 cells/µL | Standard Deviation 0.172 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | Day 43 (N = 8) | 0.261 1000 cells/µL | Standard Deviation 0.219 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | Screening (N = 25) | 0.254 1000 cells/µL | Standard Deviation 0.16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | Day 1 Prior (N = 24) | 0.152 1000 cells/µL | Standard Deviation 0.128 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | End of Infusion (N = 9) | 0.241 1000 cells/µL | Standard Deviation 0.254 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | End of Core Study (N = 6) | 0.375 1000 cells/µL | Standard Deviation 0.251 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 3-Month Follow-up (N = 5) | 0.371 1000 cells/µL | Standard Deviation 0.216 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 6-Month Follow-up (N = 6) | 0.371 1000 cells/µL | Standard Deviation 0.237 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 9-Month Follow-up (N = 4) | 0.309 1000 cells/µL | Standard Deviation 0.184 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 12-Month Follow-up (N = 4) | 0.399 1000 cells/µL | Standard Deviation 0.193 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 15-Month Follow-up (N = 3) | 0.326 1000 cells/µL | Standard Deviation 0.22 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 18-Month Follow-up (N = 3) | 0.178 1000 cells/µL | Standard Deviation 0.042 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 21-Month Follow-up (N = 21) | 0.373 1000 cells/µL | Standard Deviation 0.279 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell Count | 24-Month Follow-up (N = 3) | 0.258 1000 cells/µL | Standard Deviation 0.248 |
Secondary
CD4+ T-Cells as a Percentage of All Lymphocytes
CD4+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | Screening (N = 25) | 33 percentage of lymphocytes | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | Day 1 Prior (N = 24) | 28 percentage of lymphocytes | Standard Deviation 14 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | Day 8 (N = 21) | 32 percentage of lymphocytes | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | Day 15 (N = 16) | 29 percentage of lymphocytes | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | Day 29 (N = 11) | 34 percentage of lymphocytes | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | Day 43 (N = 8) | 30 percentage of lymphocytes | Standard Deviation 12 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | End of Infusion (N = 9) | 28 percentage of lymphocytes | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | End of Core Study (N = 6) | 32 percentage of lymphocytes | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 3-Month Follow-up (N = 5) | 33 percentage of lymphocytes | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 6-Month Follow-up (N = 6) | 30 percentage of lymphocytes | Standard Deviation 10 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 9-Month Follow-up (N = 4) | 31 percentage of lymphocytes | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 12-Month Follow-up (N = 4) | 35 percentage of lymphocytes | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 15-Month Follow-up (N = 3) | 31 percentage of lymphocytes | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 18-Month Follow-up (N = 3) | 32 percentage of lymphocytes | Standard Deviation 6 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 21-Month Follow-up (N = 21) | 29 percentage of lymphocytes | Standard Deviation 4 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cells as a Percentage of All Lymphocytes | 24-Month Follow-up (N = 3) | 34 percentage of lymphocytes | Standard Deviation 8 |
Secondary
CD4+ T-Cell to CD8+ T-Cell Ratio
CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | Screening (N = 25) | 1.32 ratio | Standard Deviation 1.19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | Day 1 Prior (N = 24) | 1.16 ratio | Standard Deviation 1.45 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | Day 8 (N = 21) | 1.20 ratio | Standard Deviation 0.96 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | Day 15 (N = 16) | 1.03 ratio | Standard Deviation 0.71 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | Day 29 (N = 11) | 1.43 ratio | Standard Deviation 1.08 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | Day 43 (N = 8) | 0.96 ratio | Standard Deviation 0.53 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | End of Infusion (N = 9) | 1.09 ratio | Standard Deviation 1 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | End of Core Study (N = 6) | 1.03 ratio | Standard Deviation 0.8 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 3-Month Follow-up (N = 5) | 1.18 ratio | Standard Deviation 0.79 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 6-Month Follow-up (N = 6) | 1.10 ratio | Standard Deviation 0.7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 9-Month Follow-up (N = 4) | 1.53 ratio | Standard Deviation 1.25 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 12-Month Follow-up (N = 4) | 1.70 ratio | Standard Deviation 1.47 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 15-Month Follow-up (N = 3) | 1.47 ratio | Standard Deviation 0.81 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 18-Month Follow-up (N = 3) | 2.23 ratio | Standard Deviation 1.7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 21-Month Follow-up (N = 21) | 1.85 ratio | Standard Deviation 1.34 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ T-Cell to CD8+ T-Cell Ratio | 24-Month Follow-up (N = 3) | 1.73 ratio | Standard Deviation 1.21 |
Secondary
CD4+ TCM Cells as a Percentage of All CD4+ T-Cells
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Screening (N = 25) | 18 percentage of CD4+ T-cells | Standard Deviation 12 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Day 1 Prior (N = 24) | 20 percentage of CD4+ T-cells | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Day 8 (N = 21) | 19 percentage of CD4+ T-cells | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Day 15 (N = 16) | 14 percentage of CD4+ T-cells | Standard Deviation 12 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Day 29 (N = 11) | 13 percentage of CD4+ T-cells | Standard Deviation 10 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | Day 43 (N = 8) | 13 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | End of Infusion (N = 9) | 15 percentage of CD4+ T-cells | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | End of Core Study (N = 6) | 14 percentage of CD4+ T-cells | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 3-Month Follow-up (N = 5) | 6 percentage of CD4+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 6-Month Follow-up (N = 6) | 9 percentage of CD4+ T-cells | Standard Deviation 4 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 9-Month Follow-up (N = 4) | 11 percentage of CD4+ T-cells | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 12-Month Follow-up (N = 4) | 18 percentage of CD4+ T-cells | Standard Deviation 16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 15-Month Follow-up (N = 3) | 13 percentage of CD4+ T-cells | Standard Deviation 6 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 18-Month Follow-up (N = 3) | 18 percentage of CD4+ T-cells | Standard Deviation 14 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 21-Month Follow-up (N = 21) | 14 percentage of CD4+ T-cells | Standard Deviation 4 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TCM Cells as a Percentage of All CD4+ T-Cells | 24-Month Follow-up (N = 3) | 12 percentage of CD4+ T-cells | Standard Deviation 11 |
Secondary
CD4+ TEM Cells as a Percentage of All CD4+ T-Cells
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Screening (N = 25) | 41 percentage of CD4+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Day 1 Prior (N = 24) | 39 percentage of CD4+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Day 8 (N = 21) | 36 percentage of CD4+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Day 15 (N = 16) | 46 percentage of CD4+ T-cells | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Day 29 (N = 11) | 34 percentage of CD4+ T-cells | Standard Deviation 20 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | Day 43 (N = 8) | 39 percentage of CD4+ T-cells | Standard Deviation 26 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | End of Infusion (N = 9) | 41 percentage of CD4+ T-cells | Standard Deviation 24 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | End of Core Study (N = 6) | 41 percentage of CD4+ T-cells | Standard Deviation 24 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 3-Month Follow-up (N = 5) | 46 percentage of CD4+ T-cells | Standard Deviation 26 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 6-Month Follow-up (N = 6) | 41 percentage of CD4+ T-cells | Standard Deviation 21 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 9-Month Follow-up (N = 4) | 42 percentage of CD4+ T-cells | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 12-Month Follow-up (N = 4) | 40 percentage of CD4+ T-cells | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 15-Month Follow-up (N = 3) | 46 percentage of CD4+ T-cells | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 18-Month Follow-up (N = 3) | 43 percentage of CD4+ T-cells | Standard Deviation 12 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 21-Month Follow-up (N = 21) | 45 percentage of CD4+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD4+ TEM Cells as a Percentage of All CD4+ T-Cells | 24-Month Follow-up (N = 3) | 51 percentage of CD4+ T-cells | Standard Deviation 22 |
Secondary
CD8+ Effector Memory T-Cell (TEM) Count
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | Screening (N = 25) | 0.127 1000 cells/µL | Standard Deviation 0.162 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | Day 1 Prior (N = 24) | 0.075 1000 cells/µL | Standard Deviation 0.066 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | Day 8 (N = 21) | 0.065 1000 cells/µL | Standard Deviation 0.058 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | Day 15 (N = 16) | 0.045 1000 cells/µL | Standard Deviation 0.053 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | Day 29 (N = 11) | 0.067 1000 cells/µL | Standard Deviation 0.039 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | Day 43 (N = 8) | 0.135 1000 cells/µL | Standard Deviation 0.108 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | End of Infusion (N = 9) | 0.128 1000 cells/µL | Standard Deviation 0.077 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | End of Core Study (N = 6) | 0.180 1000 cells/µL | Standard Deviation 0.089 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 3-Month Follow-up (N = 5) | 0.146 1000 cells/µL | Standard Deviation 0.071 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 6-Month Follow-up (N = 6) | 0.179 1000 cells/µL | Standard Deviation 0.158 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 9-Month Follow-up (N = 4) | 0.116 1000 cells/µL | Standard Deviation 0.061 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 12-Month Follow-up (N = 4) | 0.174 1000 cells/µL | Standard Deviation 0.162 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 15-Month Follow-up (N = 3) | 0.095 1000 cells/µL | Standard Deviation 0.025 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 18-Month Follow-up (N = 3) | 0.049 1000 cells/µL | Standard Deviation 0.027 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 21-Month Follow-up (N = 21) | 0.085 1000 cells/µL | Standard Deviation 0.013 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Effector Memory T-Cell (TEM) Count | 24-Month Follow-up (N = 3) | 0.054 1000 cells/µL | Standard Deviation 0.027 |
Secondary
CD8+ Naive T-Cell Count
CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | Screening (N = 25) | 0.029 1000 cells/µL | Standard Deviation 0.043 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | Day 1 Prior (N = 24) | 0.024 1000 cells/µL | Standard Deviation 0.05 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | Day 8 (N = 21) | 0.010 1000 cells/µL | Standard Deviation 0.012 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | Day 15 (N = 16) | 0.006 1000 cells/µL | Standard Deviation 0.005 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | Day 29 (N = 11) | 0.012 1000 cells/µL | Standard Deviation 0.014 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | Day 43 (N = 8) | 0.019 1000 cells/µL | Standard Deviation 0.036 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | End of Infusion (N = 9) | 0.011 1000 cells/µL | Standard Deviation 0.015 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | End of Core Study (N = 6) | 0.023 1000 cells/µL | Standard Deviation 0.018 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 3-Month Follow-up (N = 5) | 0.011 1000 cells/µL | Standard Deviation 0.007 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 6-Month Follow-up (N = 6) | 0.020 1000 cells/µL | Standard Deviation 0.022 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 9-Month Follow-up (N = 4) | 0.011 1000 cells/µL | Standard Deviation 0.012 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 12-Month Follow-up (N = 4) | 0.011 1000 cells/µL | Standard Deviation 0.009 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 15-Month Follow-up (N = 3) | 0.014 1000 cells/µL | Standard Deviation 0.011 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 18-Month Follow-up (N = 3) | 0.007 1000 cells/µL | Standard Deviation 0.008 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 21-Month Follow-up (N = 21) | 0.015 1000 cells/µL | Standard Deviation 0.006 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cell Count | 24-Month Follow-up (N = 3) | 0.010 1000 cells/µL | Standard Deviation 0.009 |
Secondary
CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells
CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Screening (N = 25) | 10 percentage of CD8+ T-cells | Standard Deviation 10 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Day 1 Prior (N = 24) | 12 percentage of CD8+ T-cells | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Day 8 (N = 21) | 9 percentage of CD8+ T-cells | Standard Deviation 8 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Day 15 (N = 16) | 8 percentage of CD8+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Day 29 (N = 11) | 8 percentage of CD8+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | Day 43 (N = 8) | 6 percentage of CD8+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | End of Infusion (N = 9) | 3 percentage of CD8+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | End of Core Study (N = 6) | 6 percentage of CD8+ T-cells | Standard Deviation 6 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 3-Month Follow-up (N = 5) | 4 percentage of CD8+ T-cells | Standard Deviation 4 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 6-Month Follow-up (N = 6) | 5 percentage of CD8+ T-cells | Standard Deviation 5 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 9-Month Follow-up (N = 4) | 6 percentage of CD8+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 12-Month Follow-up (N = 4) | 6 percentage of CD8+ T-cells | Standard Deviation 6 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 15-Month Follow-up (N = 3) | 6 percentage of CD8+ T-cells | Standard Deviation 5 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 18-Month Follow-up (N = 3) | 10 percentage of CD8+ T-cells | Standard Deviation 8 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 21-Month Follow-up (N = 21) | 8 percentage of CD8+ T-cells | Standard Deviation 4 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells | 24-Month Follow-up (N = 3) | 10 percentage of CD8+ T-cells | Standard Deviation 12 |
Secondary
CD8+ T-Cell Count
CD8+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | Screening (N = 25) | 0.298 1000 cells/µL | Standard Deviation 0.256 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | Day 1 Prior (N = 24) | 0.186 1000 cells/µL | Standard Deviation 0.136 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | Day 8 (N = 21) | 0.134 1000 cells/µL | Standard Deviation 0.099 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | Day 15 (N = 16) | 0.102 1000 cells/µL | Standard Deviation 0.095 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | Day 29 (N = 11) | 0.140 1000 cells/µL | Standard Deviation 0.076 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | Day 43 (N = 8) | 0.299 1000 cells/µL | Standard Deviation 0.237 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | End of Infusion (N = 9) | 0.284 1000 cells/µL | Standard Deviation 0.195 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | End of Core Study (N = 6) | 0.438 1000 cells/µL | Standard Deviation 0.284 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 3-Month Follow-up (N = 5) | 0.381 1000 cells/µL | Standard Deviation 0.254 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 6-Month Follow-up (N = 6) | 0.403 1000 cells/µL | Standard Deviation 0.304 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 9-Month Follow-up (N = 4) | 0.225 1000 cells/µL | Standard Deviation 0.039 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 12-Month Follow-up (N = 4) | 0.310 1000 cells/µL | Standard Deviation 0.2 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 15-Month Follow-up (N = 3) | 0.214 1000 cells/µL | Standard Deviation 0.023 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 18-Month Follow-up (N = 3) | 0.105 1000 cells/µL | Standard Deviation 0.057 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 21-Month Follow-up (N = 21) | 0.185 1000 cells/µL | Standard Deviation 0.026 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cell Count | 24-Month Follow-up (N = 3) | 0.187 1000 cells/µL | Standard Deviation 0.068 |
Secondary
CD8+ T-Cells as a Percentage of All Lymphocytes
CD8+ T-cell counts were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | Screening (N = 25) | 37 percentage of lymphocytes | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | Day 1 Prior (N = 24) | 37 percentage of lymphocytes | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | Day 8 (N = 21) | 35 percentage of lymphocytes | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | Day 15 (N = 16) | 35 percentage of lymphocytes | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | Day 29 (N = 11) | 33 percentage of lymphocytes | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | Day 43 (N = 8) | 37 percentage of lymphocytes | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | End of Infusion (N = 9) | 36 percentage of lymphocytes | Standard Deviation 16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | End of Core Study (N = 6) | 43 percentage of lymphocytes | Standard Deviation 23 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 3-Month Follow-up (N = 5) | 36 percentage of lymphocytes | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 6-Month Follow-up (N = 6) | 34 percentage of lymphocytes | Standard Deviation 16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 9-Month Follow-up (N = 4) | 25 percentage of lymphocytes | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 12-Month Follow-up (N = 4) | 28 percentage of lymphocytes | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 15-Month Follow-up (N = 3) | 24 percentage of lymphocytes | Standard Deviation 9 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 18-Month Follow-up (N = 3) | 21 percentage of lymphocytes | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 21-Month Follow-up (N = 21) | 20 percentage of lymphocytes | Standard Deviation 12 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ T-Cells as a Percentage of All Lymphocytes | 24-Month Follow-up (N = 3) | 27 percentage of lymphocytes | Standard Deviation 16 |
Secondary
CD8+ TCM Cell Counts
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | Screening (N = 25) | 0.020 100 cells/µL | Standard Deviation 0.027 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | Day 1 Prior (N = 24) | 0.014 100 cells/µL | Standard Deviation 0.021 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | Day 8 (N = 21) | 0.010 100 cells/µL | Standard Deviation 0.013 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | Day 15 (N = 16) | 0.004 100 cells/µL | Standard Deviation 0.005 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | Day 29 (N = 11) | 0.007 100 cells/µL | Standard Deviation 0.007 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | Day 43 (N = 8) | 0.012 100 cells/µL | Standard Deviation 0.015 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | End of Infusion (N = 9) | 0.009 100 cells/µL | Standard Deviation 0.009 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | End of Core Study (N = 6) | 0.016 100 cells/µL | Standard Deviation 0.023 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 3-Month Follow-up (N = 5) | 0.008 100 cells/µL | Standard Deviation 0.003 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 6-Month Follow-up (N = 6) | 0.016 100 cells/µL | Standard Deviation 0.014 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 9-Month Follow-up (N = 4) | 0.006 100 cells/µL | Standard Deviation 0.004 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 12-Month Follow-up (N = 4) | 0.010 100 cells/µL | Standard Deviation 0.01 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 15-Month Follow-up (N = 3) | 0.004 100 cells/µL | Standard Deviation 0.002 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 18-Month Follow-up (N = 3) | 0.002 100 cells/µL | Standard Deviation 0.001 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 21-Month Follow-up (N = 21) | 0.002 100 cells/µL | Standard Deviation 0.001 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cell Counts | 24-Month Follow-up (N = 3) | 0.006 100 cells/µL | Standard Deviation 0.004 |
Secondary
CD8+ TCM Cells as a Percentage of All CD8+ T-Cells
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Screening (N = 25) | 7 percentage of CD8+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Day 1 Prior (N = 24) | 8 percentage of CD8+ T-cells | Standard Deviation 11 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Day 8 (N = 21) | 10 percentage of CD8+ T-cells | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Day 15 (N = 16) | 4 percentage of CD8+ T-cells | Standard Deviation 5 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Day 29 (N = 11) | 7 percentage of CD8+ T-cells | Standard Deviation 10 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | Day 43 (N = 8) | 9 percentage of CD8+ T-cells | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | End of Infusion (N = 9) | 5 percentage of CD8+ T-cells | Standard Deviation 6 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | End of Core Study (N = 6) | 5 percentage of CD8+ T-cells | Standard Deviation 8 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 3-Month Follow-up (N = 5) | 3 percentage of CD8+ T-cells | Standard Deviation 2 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 6-Month Follow-up (N = 6) | 4 percentage of CD8+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 9-Month Follow-up (N = 4) | 3 percentage of CD8+ T-cells | Standard Deviation 2 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 12-Month Follow-up (N = 4) | 3 percentage of CD8+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 15-Month Follow-up (N = 3) | 2 percentage of CD8+ T-cells | Standard Deviation 1 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 18-Month Follow-up (N = 3) | 2 percentage of CD8+ T-cells | Standard Deviation 1 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 21-Month Follow-up (N = 21) | 1 percentage of CD8+ T-cells | Standard Deviation 0 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TCM Cells as a Percentage of All CD8+ T-Cells | 24-Month Follow-up (N = 3) | 6 percentage of CD8+ T-cells | Standard Deviation 8 |
Secondary
CD8+ TEM Cells as a Percentage of All CD8+ T-Cells
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Screening (N = 25) | 42 percentage of CD8+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Day 1 Prior (N = 24) | 42 percentage of CD8+ T-cells | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Day 8 (N = 21) | 46 percentage of CD8+ T-cells | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Day 15 (N = 16) | 43 percentage of CD8+ T-cells | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Day 29 (N = 11) | 51 percentage of CD8+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | Day 43 (N = 8) | 46 percentage of CD8+ T-cells | Standard Deviation 23 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | End of Infusion (N = 9) | 51 percentage of CD8+ T-cells | Standard Deviation 21 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | End of Core Study (N = 6) | 49 percentage of CD8+ T-cells | Standard Deviation 22 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 3-Month Follow-up (N = 5) | 47 percentage of CD8+ T-cells | Standard Deviation 23 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 6-Month Follow-up (N = 6) | 50 percentage of CD8+ T-cells | Standard Deviation 24 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 9-Month Follow-up (N = 4) | 50 percentage of CD8+ T-cells | Standard Deviation 21 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 12-Month Follow-up (N = 4) | 51 percentage of CD8+ T-cells | Standard Deviation 13 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 15-Month Follow-up (N = 3) | 46 percentage of CD8+ T-cells | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 18-Month Follow-up (N = 3) | 46 percentage of CD8+ T-cells | Standard Deviation 7 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 21-Month Follow-up (N = 21) | 46 percentage of CD8+ T-cells | Standard Deviation 1 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEM Cells as a Percentage of All CD8+ T-Cells | 24-Month Follow-up (N = 3) | 33 percentage of CD8+ T-cells | Standard Deviation 9 |
Secondary
CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells
Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Day 43 (N = 8) | 39 percentage of CD8+ T-cells | Standard Deviation 26 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | End of Infusion (N = 9) | 41 percentage of CD8+ T-cells | Standard Deviation 24 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Screening (N = 25) | 41 percentage of CD8+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Day 1 Prior (N = 24) | 39 percentage of CD8+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Day 8 (N = 21) | 36 percentage of CD8+ T-cells | Standard Deviation 19 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Day 15 (N = 16) | 46 percentage of CD8+ T-cells | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | Day 29 (N = 11) | 34 percentage of CD8+ T-cells | Standard Deviation 20 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | End of Core Study (N = 6) | 41 percentage of CD8+ T-cells | Standard Deviation 24 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 3-Month Follow-up (N = 5) | 46 percentage of CD8+ T-cells | Standard Deviation 26 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 6-Month Follow-up (N = 6) | 41 percentage of CD8+ T-cells | Standard Deviation 21 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 9-Month Follow-up (N = 4) | 42 percentage of CD8+ T-cells | Standard Deviation 18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 12-Month Follow-up (N = 4) | 40 percentage of CD8+ T-cells | Standard Deviation 15 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 15-Month Follow-up (N = 3) | 46 percentage of CD8+ T-cells | Standard Deviation 17 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 18-Month Follow-up (N = 3) | 43 percentage of CD8+ T-cells | Standard Deviation 12 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 21-Month Follow-up (N = 21) | 45 percentage of CD8+ T-cells | Standard Deviation 3 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells | 24-Month Follow-up (N = 3) | 51 percentage of CD8+ T-cells | Standard Deviation 22 |
Secondary
CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count
Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Screening (N = 25) | 0.123 1000 cells/µL | Standard Deviation 0.099 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Day 1 Prior (N = 24) | 0.072 1000 cells/µL | Standard Deviation 0.069 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Day 8 (N = 21) | 0.051 1000 cells/µL | Standard Deviation 0.042 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Day 15 (N = 16) | 0.047 1000 cells/µL | Standard Deviation 0.048 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Day 29 (N = 11) | 0.058 1000 cells/µL | Standard Deviation 0.05 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | Day 43 (N = 8) | 0.132 1000 cells/µL | Standard Deviation 0.126 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | End of Infusion (N = 9) | 0.135 1000 cells/µL | Standard Deviation 0.131 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | End of Core Study (N = 6) | 0.226 1000 cells/µL | Standard Deviation 0.249 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 3-Month Follow-up (N = 5) | 0.214 1000 cells/µL | Standard Deviation 0.22 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 6-Month Follow-up (N = 6) | 0.187 1000 cells/µL | Standard Deviation 0.182 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 9-Month Follow-up (N = 4) | 0.094 1000 cells/µL | Standard Deviation 0.046 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 12-Month Follow-up (N = 4) | 0.117 1000 cells/µL | Standard Deviation 0.065 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 15-Month Follow-up (N = 3) | 0.099 1000 cells/µL | Standard Deviation 0.041 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 18-Month Follow-up (N = 3) | 0.047 1000 cells/µL | Standard Deviation 0.035 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 21-Month Follow-up (N = 21) | 0.086 1000 cells/µL | Standard Deviation 0.016 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count | 24-Month Follow-up (N = 3) | 0.100 1000 cells/µL | Standard Deviation 0.084 |
Secondary
Duration of Complete Response
The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time frame: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Population: Efficacy set with a best overall response of CR during the first treatment cycle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Duration of Complete Response | NA months |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Duration of Complete Response | NA months |
Secondary
Duration of Objective Response
The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time frame: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Population: Efficacy set with an overall objective response of CR or PR during the first treatment cycle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Duration of Objective Response | 8.7 months |
| Cohort 2: Blinatumomab 112 μg/d | Duration of Objective Response | NA months |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Duration of Objective Response | 4.0 months |
Secondary
Duration of Partial Response
The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time frame: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Population: Efficacy set with a best overall response of PR during the first treatment cycle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Duration of Partial Response | 3.3 months |
| Cohort 2: Blinatumomab 112 μg/d | Duration of Partial Response | NA months |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Duration of Partial Response | 2.0 months |
Secondary
Granulocyte Count
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | Screening (N = 25) | 4.968 1000 cells/µL | Standard Deviation 3.187 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | Day 1 Prior (N = 24) | 4.910 1000 cells/µL | Standard Deviation 2.425 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | Day 8 (N = 21) | 6.235 1000 cells/µL | Standard Deviation 2.881 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | Day 15 (N = 16) | 5.935 1000 cells/µL | Standard Deviation 2.387 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | Day 29 (N = 11) | 2.974 1000 cells/µL | Standard Deviation 2.019 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | Day 43 (N = 8) | 3.457 1000 cells/µL | Standard Deviation 3.395 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | End of Infusion (N = 9) | 3.353 1000 cells/µL | Standard Deviation 2.134 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | End of Core Study (N = 6) | 5.080 1000 cells/µL | Standard Deviation 3.012 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 3-Month Follow-up (N = 5) | 3.182 1000 cells/µL | Standard Deviation 1.117 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 6-Month Follow-up (N = 6) | 3.594 1000 cells/µL | Standard Deviation 0.95 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 9-Month Follow-up (N = 4) | 2.925 1000 cells/µL | Standard Deviation 0.675 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 12-Month Follow-up (N = 4) | 4.111 1000 cells/µL | Standard Deviation 1.382 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 15-Month Follow-up (N = 3) | 3.258 1000 cells/µL | Standard Deviation 0.745 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 18-Month Follow-up (N = 3) | 5.612 1000 cells/µL | Standard Deviation 1.713 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 21-Month Follow-up (N = 21) | 3.729 1000 cells/µL | Standard Deviation 0.352 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Granulocyte Count | 24-Month Follow-up (N = 3) | 3.563 1000 cells/µL | Standard Deviation 0.711 |
Secondary
Leukocyte Counts
Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | Screening (N = 25) | 6.376 1000 cells/µL | Standard Deviation 3.284 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | Day 1 Prior (N = 24) | 5.729 1000 cells/µL | Standard Deviation 2.891 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | Day 8 (N = 21) | 6.819 1000 cells/µL | Standard Deviation 3.201 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | Day 15 (N = 16) | 6.400 1000 cells/µL | Standard Deviation 2.486 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | Day 29 (N = 11) | 3.764 1000 cells/µL | Standard Deviation 2.16 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | Day 43 (N = 8) | 4.950 1000 cells/µL | Standard Deviation 3.819 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | End of Infusion (N = 9) | 4.611 1000 cells/µL | Standard Deviation 2.114 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | End of Core Study (N = 6) | 6.850 1000 cells/µL | Standard Deviation 2.818 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 3-Month Follow-up (N = 5) | 4.820 1000 cells/µL | Standard Deviation 1.616 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 6-Month Follow-up (N = 6) | 5.183 1000 cells/µL | Standard Deviation 1.38 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 9-Month Follow-up (N = 4) | 4.425 1000 cells/µL | Standard Deviation 0.854 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 12-Month Follow-up (N = 4) | 5.700 1000 cells/µL | Standard Deviation 1.424 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 15-Month Follow-up (N = 3) | 4.767 1000 cells/µL | Standard Deviation 0.874 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 18-Month Follow-up (N = 3) | 6.467 1000 cells/µL | Standard Deviation 1.779 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 21-Month Follow-up (N = 21) | 5.450 1000 cells/µL | Standard Deviation 0.495 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Leukocyte Counts | 24-Month Follow-up (N = 3) | 4.533 1000 cells/µL | Standard Deviation 1.069 |
Secondary
Lymphocyte Counts
Lymphocyte counts were analyzed by differential blood count analysis.
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | Screening (N = 25) | 0.779 1000 cells/µL | Standard Deviation 0.425 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | Day 1 Prior (N = 24) | 0.491 1000 cells/µL | Standard Deviation 0.259 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | Day 8 (N = 21) | 0.382 1000 cells/µL | Standard Deviation 0.215 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | Day 15 (N = 16) | 0.277 1000 cells/µL | Standard Deviation 0.165 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | Day 29 (N = 11) | 0.472 1000 cells/µL | Standard Deviation 0.273 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | Day 43 (N = 8) | 0.847 1000 cells/µL | Standard Deviation 0.511 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | End of Infusion (N = 9) | 0.767 1000 cells/µL | Standard Deviation 0.505 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | End of Core Study (N = 6) | 1.060 1000 cells/µL | Standard Deviation 0.489 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 3-Month Follow-up (N = 5) | 1.053 1000 cells/µL | Standard Deviation 0.421 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 6-Month Follow-up (N = 6) | 1.120 1000 cells/µL | Standard Deviation 0.621 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 9-Month Follow-up (N = 4) | 1.048 1000 cells/µL | Standard Deviation 0.381 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 12-Month Follow-up (N = 4) | 1.120 1000 cells/µL | Standard Deviation 0.449 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 15-Month Follow-up (N = 3) | 0.998 1000 cells/µL | Standard Deviation 0.527 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 18-Month Follow-up (N = 3) | 0.565 1000 cells/µL | Standard Deviation 0.18 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 21-Month Follow-up (N = 21) | 1.205 1000 cells/µL | Standard Deviation 0.839 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Lymphocyte Counts | 24-Month Follow-up (N = 3) | 0.737 1000 cells/µL | Standard Deviation 0.478 |
Secondary
Monocyte Counts
Time frame: Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Population: Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | Screening (N = 25) | 0.638 1000 cells/µL | Standard Deviation 0.415 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | Day 1 Prior (N = 24) | 0.300 1000 cells/µL | Standard Deviation 0.565 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | Day 8 (N = 21) | 0.202 1000 cells/µL | Standard Deviation 0.386 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | Day 15 (N = 16) | 0.188 1000 cells/µL | Standard Deviation 0.317 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | Day 29 (N = 11) | 0.318 1000 cells/µL | Standard Deviation 0.185 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | Day 43 (N = 8) | 0.646 1000 cells/µL | Standard Deviation 0.375 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | End of Infusion (N = 9) | 0.473 1000 cells/µL | Standard Deviation 0.241 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | End of Core Study (N = 6) | 0.711 1000 cells/µL | Standard Deviation 0.569 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 3-Month Follow-up (N = 5) | 0.585 1000 cells/µL | Standard Deviation 0.28 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 6-Month Follow-up (N = 6) | 0.487 1000 cells/µL | Standard Deviation 0.239 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 9-Month Follow-up (N = 4) | 0.452 1000 cells/µL | Standard Deviation 0.112 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 12-Month Follow-up (N = 4) | 0.469 1000 cells/µL | Standard Deviation 0.061 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 15-Month Follow-up (N = 3) | 0.511 1000 cells/µL | Standard Deviation 0.053 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 18-Month Follow-up (N = 3) | 0.290 1000 cells/µL | Standard Deviation 0.123 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 21-Month Follow-up (N = 21) | 0.516 1000 cells/µL | Standard Deviation 0.008 |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Monocyte Counts | 24-Month Follow-up (N = 3) | 0.234 1000 cells/µL | Standard Deviation 0.176 |
Secondary
Number of Participants With Adverse Events
Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. An adverse event or suspected adverse drug reaction was considered serious if it resulted in one of the following outcomes: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions; * Was a congenital anomaly or birth defect; * Was a medically important condition. The Investigator used medical judgment to determine whether there was a causal relationship (ie, related \[reasonably possible\] or unrelated \[not reasonably possible\]) between an adverse event and blinatumomab.
Time frame: From the first dose of blinatumomab until up to 30 days after the last dose or until the data cut-off date of 10 July 2014, whichever occurred first; the overall median duration of treatment exposure was 46.8 days.
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | AE of Grade ≥ 4 | 0 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE Grade ≥ 4 | 0 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Serious related adverse events | 5 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE led to discontinuation of study drug | 2 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Serious adverse event (SAE) | 9 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE led to interruption of study drug | 3 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Led to discontinuation of study drug | 3 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Fatal adverse events | 0 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | AE of Grade ≥ 3 | 9 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Led to interruption of study drug | 4 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related adverse events | 9 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Any adverse event (AE) | 9 participants |
| Cohort 1: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE Grade ≥ 3 | 5 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Led to interruption of study drug | 1 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | AE of Grade ≥ 3 | 2 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Related AE Grade ≥ 4 | 1 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | AE of Grade ≥ 4 | 2 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Fatal adverse events | 0 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Serious related adverse events | 2 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Any adverse event (AE) | 2 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Led to discontinuation of study drug | 1 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Related AE led to discontinuation of study drug | 1 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Related AE Grade ≥ 3 | 2 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Related adverse events | 2 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Related AE led to interruption of study drug | 1 participants |
| Cohort 2: Blinatumomab 112 μg/d | Number of Participants With Adverse Events | Serious adverse event (SAE) | 2 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE led to interruption of study drug | 3 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Any adverse event (AE) | 14 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | AE of Grade ≥ 3 | 13 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | AE of Grade ≥ 4 | 6 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Serious adverse event (SAE) | 12 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Led to discontinuation of study drug | 2 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Led to interruption of study drug | 6 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related adverse events | 11 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE Grade ≥ 3 | 5 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE Grade ≥ 4 | 2 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Serious related adverse events | 3 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Related AE led to discontinuation of study drug | 2 participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Number of Participants With Adverse Events | Fatal adverse events | 2 participants |
Secondary
Overall Survival (OS)
The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed.
Time frame: From the first infusion of blinatumomab until the end of study; median time on follow-up for overall survival was 26.6 months.
Population: Efficacy set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Overall Survival (OS) | 20.1 months |
| Cohort 2: Blinatumomab 112 μg/d | Overall Survival (OS) | NA months |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Overall Survival (OS) | 3.6 months |
Secondary
Percentage of Participants With a Best Overall Response of Complete Response
Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Complete response is defined as the disappearance of all evidence of disease.
Time frame: During the first 8 weeks
Population: Efficacy set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Percentage of Participants With a Best Overall Response of Complete Response | 28.6 percentage of participants |
| Cohort 2: Blinatumomab 112 μg/d | Percentage of Participants With a Best Overall Response of Complete Response | 0 percentage of participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Percentage of Participants With a Best Overall Response of Complete Response | 15.4 percentage of participants |
Secondary
Percentage of Participants With a Best Overall Response of Partial Response
Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (\<50% decrease in size of masses) of measureable disease and no new sites.
Time frame: During the first 8 weeks
Population: Efficacy set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Percentage of Participants With a Best Overall Response of Partial Response | 28.6 percentage of participants |
| Cohort 2: Blinatumomab 112 μg/d | Percentage of Participants With a Best Overall Response of Partial Response | 100.0 percentage of participants |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Percentage of Participants With a Best Overall Response of Partial Response | 15.4 percentage of participants |
Secondary
Progression-free Survival (PFS)
The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment.
Time frame: From first infusion of blinatumomab until the end of study; median time on follow-up for PFS was 27.0 months.
Population: Efficacy set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab 9/28/112 μg/d | Progression-free Survival (PFS) | 3.7 months |
| Cohort 2: Blinatumomab 112 μg/d | Progression-free Survival (PFS) | NA months |
| Cohort 3: Blinatumomab 9/28/112 μg/d | Progression-free Survival (PFS) | 1.6 months |