Diffuse Large B-cell Lymphoma
Conditions
Keywords
Diffuse Large B-cell Lymphoma, bendamustine, rituximab, combination therapy, CD19 monoclonal antibody, transplant ineligible
Brief summary
The purpose of the study is to compare the safety and efficacy of Tafasitamab with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.
Detailed description
This is a randomised, two-arm, multicentre, open-label phase II/III efficacy and safety study of Tafasitamab in combination with BEN versus RTX in combination with BEN given to adult patients who have relapsed after or are refractory to at least one but no more than three prior systemic therapies and have failed, or are not candidates for HDC and ASCT, and have thus exhausted their therapeutic options of demonstrated clinical benefit. At least one prior therapy line must have included a CD20-targeted therapy.
Interventions
DRUGRituximab (RTX)
Rituximab: Dose: 375 mg/m2 IV
DRUGTafasitamab
Tafasitamab: Tafasitamab dose: 12 mg/kg intravenously (IV)
DRUGBendamustine (BEN)
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessor: blinding on treatment group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Histologically confirmed diagnosis, according to the World Health Organization (WHO, 2008) classification, of: DLBCL NOS, THRLBCL, EBV-positive DLBCL, composite lymphoma with a DLBCL component with a DLBCL relapse subsequent to DLBCL treatment, disease transformed from an earlier diagnosis of low grade lymphoma (i.e. an indolent pathology such as follicular lymphoma, marginal zone lymphoma) into DLBCL with a DLBCL relapse subsequent to DLBCL treatment. 3. Fresh tumour tissue for central pathology review must be provided as an adjunct to participation in this study. Should it not be possible to obtain a fresh tumour tissue sample, archival paraffin embedded tumour tissue acquired ≤3 years prior to screening for this protocol must be available for this purpose. 4. Patients must have: 1. relapsed or refractory DLBCL 2. at least one bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of ≥1.5 cm and greatest perpendicular diameter of ≥1.0 cm at baseline. The lesion must be positive on PET scan 3. received at least one, but no more than three previous systemic therapy lines for the treatment of DLBCL. At least one previous therapy line must have included a CD20-targeted. 4. ECOG 0 to 2 5. Patients after failure of ASCT or patients considered in the opinion of the investigator currently not eligible for HDC with subsequent ASCT. 6. Patients must meet the following laboratory criteria at Screening: 1. ANC ≥1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL) 2. PLTs ≥90 × 109/L (unless secondary to bone marrow involvement by DLBCL) and absence of active bleeding 3. total serum bilirubin ≤2.5 × ULN unless secondary to Gilbert's syndrome (or pattern consistent with Gilbert's) or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is ≤5 x ULN 4. ALT, AST and AP ≤3 × ULN or \<5 × ULN in cases of documented liver involvement by lymphoma 5. serum creatinine ≤2.0 x ULN or creatinine clearance must be ≥40 mL/min calculated using a standard Cockcroft-Gault formula (Cockroft & Gault, 1976) 7. For a female of childbearing potential (FCBP), a negative pregnancy test must be confirmed before enrolment. An FCBP must commit to take highly effective contraceptive precautions without interruption during the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. An FCBP must refrain from breastfeeding and donating blood or oocytes during the course of the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. Restrictions concerning blood donations apply as well to females who are not of childbearing potential. 8. Males must use an effective barrier method of contraception without interruption during the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later, if the patient is sexually active with an FCBP. Males must refrain from donating blood or sperm during study participation and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. 9. In the opinion of the investigator, the patients must: 1. be able to comply with all study-related procedures, medication use, and evaluations 2. be able to understand and give informed consent 3. not be considered to be potentially unreliable and/or not cooperative.
Exclusion criteria
1. Patients who have: any other histological type of lymphoma including, e.g., primary mediastinal (thymic) large B-cell lymphoma (PMBL) or Burkitt's lymphoma, primary refractory DLBCL, patients with known double/triple hit DLBCL genetics, CNS lymphoma involvement in present or past medical history 2. Patients who had a major surgery less than 30 days prior to Day 1 dosing 3. Patients who have, within 14 days prior to Day 1 dosing: 1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma-specific therapy 2. received live vaccines 3. required parenteral antimicrobial therapy for active, intercurrent systemic infections 4. Patients who: 1. in the opinion of the investigator, have not recovered sufficiently from the adverse toxic effects of prior therapies, major surgeries or significant traumatic injuries 2. were previously treated with CD19-targeted therapy or BEN 3. have a history of previous severe allergic reactions to compounds of similar biological or chemical composition to Tafasitamab, RTX, murine proteins or BEN, or the excipients contained in the study drug formulations 4. have undergone ASCT within a period of ≤3 months prior to signing the informed consent form. Patients who have a more distant history of ASCT must exhibit full haematological recovery before enrolment into the study. 5. have undergone previous allogeneic stem cell transplantation 6. concurrently use other anticancer or experimental treatments 5. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for ≥3 years prior to Screening. Exceptions to the ≥3-year time limit include history of the following: 1. basal cell carcinoma of the skin 2. squamous cell carcinoma of the skin 3. carcinoma in situ of the cervix, breast and bladder f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis \[TNM\] stage of T1a or T1b) 6. Patients with: 1. positive hepatitis B and/or C serology 2. known seropositivity for or history of active viral infection with HIV 3. evidence of active, severe uncontrolled systemic infections or sepsis 4. a history or evidence of severely immunocompromised state 5. a history or evidence of severe hepatic impairment (total serum bilirubin \> 3 mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma 6. a history or evidence of clinically significant cardiovascular, cerebrovascular, CNS and/or other disease that, in the investigator's opinion, would preclude participation in the study or compromise the patient's ability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | up to 41.4 months | Progression-free survival was defined as the time from randomization to tumor progression or death from any cause. |
| Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | up to 46.5 months | Progression-free survival was defined as the time from randomization to tumor progression or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | up to 40.2 months | Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. |
| Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | up to 44.7 months | Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. |
| Kaplan-Meier Estimate of Overall Survival in the Overall Population | up to 50.0 months | Overall survival was defined as the time (in months) from randomization until death from any cause. |
| Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup | up to 50.6 months | Overall survival was defined as the time (in months) from randomization until death from any cause. |
| Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | up to 77 months | DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD) based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or progressive disease (PD; any new lesion or an increase by ≥50% of previously involved sites from nadir). |
| DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | up to 77 months | DCR was defined as the percentage of participants with a CR, PR, or SD based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or PD (any new lesion or an increase by ≥50% of previously involved sites from nadir). |
| Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | up to 25.8 months | Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation. |
| Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | up to 40.6 months | Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation. |
| Kaplan-Meier Estimate of Time to Next Treatment in the Overall Population | up to 59.4 months | Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first. |
| Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | up to 77 months | Best ORR was defined as the percentage of patients with complete response (CR) or partial response (PR) based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 77 months | An adverse event was defined as any untoward medical occurrence in a participant administered a medicinal product, which did not necessarily have a causal relationship to this treatment. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it was considered related to that study drug. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug. |
| Number of Participants With Any Grade 3 or Higher TEAE | up to 77 months | AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (or higher). Grade 1: mild; asymptomatic or mild symptoms. Grade 2: moderate. Grade 3: severe or medically significant but not immediately life threatening. Grade 4: life-threatening consequences. Grade 5: death. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug. |
| Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; End of Treatment (EOT) (up to 77 months) | The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual. |
| Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; End of Treatment (EOT) (up to 77 months) | The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual. |
| Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline; End of Treatment (EOT) (up to 77 months) | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. |
| Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population | Baseline; End of Treatment (EOT) (up to 77 months) | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. |
| Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; End of Treatment (EOT) (up to 77 months) | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. |
| Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; End of Treatment (EOT) (up to 77 months) | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. |
| Tafasitamab Serum Concentrations | pre-dose: Cycle 1 Days 1, 2, 3, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15, Cycles 4, 5, 6, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 Day 1. 1 hour post-dose: Cycle 1 Days 1, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15 | Blood samples were collected for the assessment of serum concentrations of tafasitamab. |
| Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup | up to 70.1 months | Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first. |
| Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | up to 77 months | Best ORR was defined as the percentage of patients with CR or PR based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. |
Countries
Australia, Austria, Canada, Croatia, Czechia, Finland, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, Romania, Serbia, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
This study was conducted at 138 study centers in: Australia, Austria, Canada, Croatia, Czech Republic, Finland, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, Romania, Serbia, South Korea, Spain, Singapore, Taiwan, Turkey, the United Kingdom, and the United States of America.
Participants by arm
| Arm | Count |
|---|---|
| Tafasitamab + Bendamustine Participants received intravenous (IV) tafasitamab 12.0 milligrams per kilogram (mg/kg) in combination with IV bendamustine 90 mg/meters squared (m\^2) in 28-day cycles for a maximum of 6 cycles. During Cycles 1 to 3, participants received tafastiamab on Days 1, 8, 15, and 22, plus a loading dose on Day 4 of Cycle 1. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first. | 226 |
| Rituximab + Bendamustine Participants received IV rituximab 375 mg/m\^2 in combination with IV bendamustine 90 mg/m\^2 in 28-day cycles for a maximum of 6 cycles. Participants received rituximab on Day 1 of each cycle until disease progression. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first. | 227 |
| Total | 453 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 3 |
| Overall Study | Captured as Other in Database | 29 | 34 |
| Overall Study | Completed the Maximum per Protocol Treatment Period | 1 | 0 |
| Overall Study | Death | 123 | 123 |
| Overall Study | Diagnosed with COVID-19 and/or Tested Positive for Coronavirus SARS-CoV-2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 6 | 7 |
| Overall Study | Noncompliance with Study Drug | 2 | 0 |
| Overall Study | Physician Decision | 1 | 7 |
| Overall Study | Progressive Disease | 24 | 27 |
| Overall Study | Withdrawal by Subject | 26 | 25 |
Baseline characteristics
| Characteristic | Tafasitamab + Bendamustine | Rituximab + Bendamustine | Total |
|---|---|---|---|
| Age, Continuous | 70.9 years STANDARD_DEVIATION 10.36 | 70.8 years STANDARD_DEVIATION 9.92 | 70.9 years STANDARD_DEVIATION 10.13 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 41 Participants | 45 Participants | 86 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Captured as Hispanic in Database | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Captured as Other in Database | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Eurasian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized European | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Iraqi | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Applicable in Enrolled Country | 8 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 172 Participants | 171 Participants | 343 Participants |
| Sex: Female, Male Female | 96 Participants | 96 Participants | 192 Participants |
| Sex: Female, Male Male | 130 Participants | 131 Participants | 261 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 129 / 226 | 127 / 227 |
| other Total, other adverse events | 206 / 219 | 199 / 225 |
| serious Total, serious adverse events | 115 / 219 | 100 / 225 |
Outcome results
Primary
Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
Progression-free survival was defined as the time from randomization to tumor progression or death from any cause.
Time frame: up to 46.5 months
Population: Natural Killer Cell Count-Low Full Analysis Set: participants in the FAS with ≤100 NK cells/µL at Baseline. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 5.60 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 5.60 months |
p-value: 0.56895% CI: [0.586, 1.33]Inverse normal test
Primary
Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
Progression-free survival was defined as the time from randomization to tumor progression or death from any cause.
Time frame: up to 41.4 months
Population: Full Analysis Set (FAS): all participants who were randomized to either treatment arm. Participants were analyzed according to the treatment and stratification factors they were assigned to during the randomization procedure. 95% confidence intervals (CIs) (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 7.10 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 8.30 months |
p-value: 0.46895% CI: [0.837, 1.351]Inverse normal test
Secondary
Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
Best ORR was defined as the percentage of patients with complete response (CR) or partial response (PR) based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Time frame: up to 77 months
Population: Full Analysis Set. A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafasitamab + Bendamustine | Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 65.5 percentage of participants |
| Rituximab + Bendamustine | Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 61.7 percentage of participants |
95% CI: [0.812, 1.779]
Secondary
Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
Best ORR was defined as the percentage of patients with CR or PR based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Time frame: up to 77 months
Population: Natural Killer Cell Count-Low Full Analysis Set. A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafasitamab + Bendamustine | Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 64.8 percentage of participants |
| Rituximab + Bendamustine | Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 59.5 percentage of participants |
95% CI: [0.778, 3.041]
Secondary
Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup
The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Time frame: Baseline; End of Treatment (EOT) (up to 77 months)
Population: Natural Killer Cell Count-Low Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Mobility Level | 2.09 scores on a scale | Standard Deviation 0.983 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Self-care Level | 1.49 scores on a scale | Standard Deviation 0.977 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Usual Activities | 2.03 scores on a scale | Standard Deviation 1.116 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Pain/Discomfort | 2.08 scores on a scale | Standard Deviation 1.054 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Anxiety/Depression | 1.65 scores on a scale | Standard Deviation 0.803 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Mobility Level | 0.55 scores on a scale | Standard Deviation 1.08 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Self-care Level | 0.53 scores on a scale | Standard Deviation 1.08 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Usual Activities | 0.62 scores on a scale | Standard Deviation 1.392 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Pain/Discomfort | 0.40 scores on a scale | Standard Deviation 1.173 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Anxiety/Depression | 0.30 scores on a scale | Standard Deviation 1.25 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Usual Activities | 0.53 scores on a scale | Standard Deviation 1.224 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Mobility Level | 2.04 scores on a scale | Standard Deviation 1.104 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Mobility Level | 0.46 scores on a scale | Standard Deviation 1.315 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Self-care Level | 1.54 scores on a scale | Standard Deviation 0.917 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Anxiety/Depression | 0.24 scores on a scale | Standard Deviation 1.324 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Usual Activities | 2.14 scores on a scale | Standard Deviation 1.228 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Self-care Level | 0.41 scores on a scale | Standard Deviation 1.312 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Pain/Discomfort | 2.26 scores on a scale | Standard Deviation 1.06 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Pain/Discomfort | 0.05 scores on a scale | Standard Deviation 1.469 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Anxiety/Depression | 1.96 scores on a scale | Standard Deviation 1.143 |
Secondary
Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population
The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Time frame: Baseline; End of Treatment (EOT) (up to 77 months)
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Mobility Level | 1.83 scores on a scale | Standard Deviation 0.969 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Self-care Level | 1.37 scores on a scale | Standard Deviation 0.771 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Usual Activities | 1.97 scores on a scale | Standard Deviation 1.086 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Pain/Discomfort | 2.04 scores on a scale | Standard Deviation 1.045 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Anxiety/Depression | 1.67 scores on a scale | Standard Deviation 0.844 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Mobility Level | 0.47 scores on a scale | Standard Deviation 1.076 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Self-care Level | 0.48 scores on a scale | Standard Deviation 1.052 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Usual Activities | 0.42 scores on a scale | Standard Deviation 1.41 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Pain/Discomfort | 0.29 scores on a scale | Standard Deviation 1.102 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Anxiety/Depression | 0.33 scores on a scale | Standard Deviation 1.071 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Usual Activities | 0.31 scores on a scale | Standard Deviation 1.066 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Mobility Level | 1.94 scores on a scale | Standard Deviation 1.054 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Mobility Level | 0.25 scores on a scale | Standard Deviation 1.094 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Self-care Level | 1.44 scores on a scale | Standard Deviation 0.861 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Anxiety/Depression | 0.21 scores on a scale | Standard Deviation 1.03 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Usual Activities | 1.92 scores on a scale | Standard Deviation 1.063 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Self-care Level | 0.23 scores on a scale | Standard Deviation 0.946 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Pain/Discomfort | 2.08 scores on a scale | Standard Deviation 1.027 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | CFB at EOT, Pain/Discomfort | 0.09 scores on a scale | Standard Deviation 1.173 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population | Baseline, Anxiety/Depression | 1.73 scores on a scale | Standard Deviation 0.907 |
Secondary
Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup
The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Time frame: Baseline; End of Treatment (EOT) (up to 77 months)
Population: Natural Killer Cell Count-Low Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline | 65.87 scores on a scale | Standard Deviation 21.4 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Change from Baseline at End of Treatment | -10.75 scores on a scale | Standard Deviation 21 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline | 58.65 scores on a scale | Standard Deviation 20.7 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Change from Baseline at End of Treatment | -7.53 scores on a scale | Standard Deviation 31.4 |
Secondary
Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population
The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Time frame: Baseline; End of Treatment (EOT) (up to 77 months)
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population | Baseline | 66.22 scores on a scale | Standard Deviation 20.5 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population | Change from Baseline at End of Treatment | -8.10 scores on a scale | Standard Deviation 21.1 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population | Baseline | 66.69 scores on a scale | Standard Deviation 20.4 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population | Change from Baseline at End of Treatment | -5.47 scores on a scale | Standard Deviation 23.2 |
Secondary
Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup
The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.
Time frame: Baseline; End of Treatment (EOT) (up to 77 months)
Population: Natural Killer Cell Count-Low Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Baseline; Global Health Status/QoL Scale | -6.57 scores on a scale | Standard Deviation 23.7 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Pain | 28.88 scores on a scale | Standard Deviation 32.38 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Baseline; Physical Functioning | -15.29 scores on a scale | Standard Deviation 25.83 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Physical Functioning | 68.60 scores on a scale | Standard Deviation 24.73 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Role Functioning | -19.61 scores on a scale | Standard Deviation 37.07 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Dyspnoea | 21.32 scores on a scale | Standard Deviation 25.52 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Emotional Functioning | -4.81 scores on a scale | Standard Deviation 28.02 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Social Functioning | 73.84 scores on a scale | Standard Deviation 27 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Cognitive Functioning | -7.69 scores on a scale | Standard Deviation 22.01 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Insomnia | 31.78 scores on a scale | Standard Deviation 30.64 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Social Functioning | -16.67 scores on a scale | Standard Deviation 27.42 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Emotional Functioning | 76.10 scores on a scale | Standard Deviation 22.32 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Fatigue | 13.51 scores on a scale | Standard Deviation 31.69 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Loss of Appetite | 21.32 scores on a scale | Standard Deviation 27.49 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Nausea and Vomiting | 5.66 scores on a scale | Standard Deviation 14.78 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Fatigue | 39.02 scores on a scale | Standard Deviation 26.61 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Pain | 8.65 scores on a scale | Standard Deviation 33.09 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Constipation | 17.83 scores on a scale | Standard Deviation 26.91 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Dyspnoea | 9.15 scores on a scale | Standard Deviation 37.17 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Role Functioning | 65.89 scores on a scale | Standard Deviation 31.61 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Insomnia | 5.88 scores on a scale | Standard Deviation 35.09 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Diarrhoea | 7.75 scores on a scale | Standard Deviation 16.71 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Loss of Appetite | 20.26 scores on a scale | Standard Deviation 41.14 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Nausea and Vomiting | 6.20 scores on a scale | Standard Deviation 14.24 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Constipation | 5.88 scores on a scale | Standard Deviation 32.46 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Financial Impact | 13.57 scores on a scale | Standard Deviation 25.25 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Diarrhoea | 5.77 scores on a scale | Standard Deviation 21.61 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Cognitive Functioning | 84.88 scores on a scale | Standard Deviation 18.72 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Financial Impact | 2.56 scores on a scale | Standard Deviation 17.27 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Global Health Status/QoL Scale | 57.66 scores on a scale | Standard Deviation 22.37 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Financial Impact | 7.32 scores on a scale | Standard Deviation 26.37 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Global Health Status/QoL Scale | 52.59 scores on a scale | Standard Deviation 24.13 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Physical Functioning | 64.30 scores on a scale | Standard Deviation 26.46 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Role Functioning | 60.59 scores on a scale | Standard Deviation 33.63 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Emotional Functioning | 67.61 scores on a scale | Standard Deviation 28.71 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Cognitive Functioning | 77.03 scores on a scale | Standard Deviation 23.84 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline; Social Functioning | 67.34 scores on a scale | Standard Deviation 31.87 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Fatigue | 43.62 scores on a scale | Standard Deviation 28.01 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Nausea and Vomiting | 15.77 scores on a scale | Standard Deviation 26.44 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Pain | 34.68 scores on a scale | Standard Deviation 32.5 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Dyspnoea | 21.62 scores on a scale | Standard Deviation 28.37 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Insomnia | 36.49 scores on a scale | Standard Deviation 33.64 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Loss of Appetite | 29.73 scores on a scale | Standard Deviation 36 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Constipation | 16.67 scores on a scale | Standard Deviation 27.72 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Diarrhoea | 9.01 scores on a scale | Standard Deviation 22.95 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | Baseline, Financial Impact | 24.32 scores on a scale | Standard Deviation 32.78 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Baseline; Global Health Status/QoL Scale | -7.54 scores on a scale | Standard Deviation 30.84 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Baseline; Physical Functioning | -11.83 scores on a scale | Standard Deviation 33.6 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Role Functioning | -15.45 scores on a scale | Standard Deviation 41.06 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Emotional Functioning | 0.27 scores on a scale | Standard Deviation 33.98 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Cognitive Functioning | -5.95 scores on a scale | Standard Deviation 30.54 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT; Social Functioning | -2.44 scores on a scale | Standard Deviation 32.18 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Fatigue | 13.10 scores on a scale | Standard Deviation 33.19 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Nausea and Vomiting | -3.66 scores on a scale | Standard Deviation 34.86 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Pain | 7.94 scores on a scale | Standard Deviation 42.97 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Dyspnoea | 7.94 scores on a scale | Standard Deviation 32.77 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Insomnia | -1.59 scores on a scale | Standard Deviation 41.62 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Loss of Appetite | 10.32 scores on a scale | Standard Deviation 42.6 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Constipation | 0.79 scores on a scale | Standard Deviation 30.79 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup | CFB at EOT, Diarrhoea | 5.56 scores on a scale | Standard Deviation 30.28 |
Secondary
Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population
The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.
Time frame: Baseline; End of Treatment (EOT) (up to 77 months)
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Nausea and Vomiting | 5.47 scores on a scale | Standard Deviation 18.37 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Global Health Status/QoL Scale | 59.19 scores on a scale | Standard Deviation 22.94 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Physical Functioning | 71.68 scores on a scale | Standard Deviation 23.05 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Role Functioning | 68.91 scores on a scale | Standard Deviation 30.84 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Emotional Functioning | 76.63 scores on a scale | Standard Deviation 22.24 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Cognitive Functioning | 82.81 scores on a scale | Standard Deviation 18.61 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Social Functioning | 74.74 scores on a scale | Standard Deviation 27.53 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Fatigue | 37.74 scores on a scale | Standard Deviation 26.69 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Nausea and Vomiting | 6.20 scores on a scale | Standard Deviation 15.26 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Pain | 28.25 scores on a scale | Standard Deviation 31.02 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Dyspnoea | 19.43 scores on a scale | Standard Deviation 25.13 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Insomnia | 30.64 scores on a scale | Standard Deviation 32.77 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Loss of Appetite | 20.27 scores on a scale | Standard Deviation 28.44 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Constipation | 15.25 scores on a scale | Standard Deviation 24.85 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Diarrhoea | 8.07 scores on a scale | Standard Deviation 17.46 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Financial Impact | 14.20 scores on a scale | Standard Deviation 24.97 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Baseline; Global Health Status/QoL Scale | -7.23 scores on a scale | Standard Deviation 22.56 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Baseline; Physical Functioning | -13.59 scores on a scale | Standard Deviation 25.48 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Role Functioning | -14.84 scores on a scale | Standard Deviation 33.87 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Emotional Functioning | -5.60 scores on a scale | Standard Deviation 24.88 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Cognitive Functioning | -7.29 scores on a scale | Standard Deviation 23.37 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Social Functioning | -14.32 scores on a scale | Standard Deviation 31.56 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Fatigue | 11.89 scores on a scale | Standard Deviation 31.49 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Insomnia | 1.30 scores on a scale | Standard Deviation 36.8 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Pain | 6.33 scores on a scale | Standard Deviation 30.42 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Dyspnoea | 9.11 scores on a scale | Standard Deviation 34.93 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Loss of Appetite | 16.15 scores on a scale | Standard Deviation 38.33 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Constipation | 5.21 scores on a scale | Standard Deviation 33.58 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Diarrhoea | 7.03 scores on a scale | Standard Deviation 28.26 |
| Tafasitamab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Financial Impact | 2.08 scores on a scale | Standard Deviation 22.04 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Financial Impact | 21.78 scores on a scale | Standard Deviation 28.26 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Nausea and Vomiting | 3.10 scores on a scale | Standard Deviation 25 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Global Health Status/QoL Scale | 59.89 scores on a scale | Standard Deviation 23.75 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Baseline; Global Health Status/QoL Scale | -7.99 scores on a scale | Standard Deviation 22.71 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Physical Functioning | 69.39 scores on a scale | Standard Deviation 24.6 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Diarrhoea | 1.38 scores on a scale | Standard Deviation 28.02 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Role Functioning | 69.53 scores on a scale | Standard Deviation 31.48 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Baseline; Physical Functioning | -7.51 scores on a scale | Standard Deviation 22.95 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Emotional Functioning | 74.79 scores on a scale | Standard Deviation 25.05 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Pain | 7.93 scores on a scale | Standard Deviation 33.11 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Cognitive Functioning | 81.41 scores on a scale | Standard Deviation 22.74 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Role Functioning | -10.88 scores on a scale | Standard Deviation 32.35 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline; Social Functioning | 73.93 scores on a scale | Standard Deviation 29.45 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Constipation | 1.60 scores on a scale | Standard Deviation 28.05 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Fatigue | 36.64 scores on a scale | Standard Deviation 27.28 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Emotional Functioning | -2.41 scores on a scale | Standard Deviation 24.83 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Nausea and Vomiting | 9.69 scores on a scale | Standard Deviation 21.25 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Dyspnoea | 8.05 scores on a scale | Standard Deviation 28.4 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Pain | 27.36 scores on a scale | Standard Deviation 30.18 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Cognitive Functioning | -4.71 scores on a scale | Standard Deviation 24.67 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Dyspnoea | 18.06 scores on a scale | Standard Deviation 25.7 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Insomnia | 2.28 scores on a scale | Standard Deviation 33.37 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Insomnia | 29.22 scores on a scale | Standard Deviation 31.87 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT; Social Functioning | -4.98 scores on a scale | Standard Deviation 27.03 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Loss of Appetite | 22.17 scores on a scale | Standard Deviation 31.87 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Financial Impact | 1.17 scores on a scale | Standard Deviation 25.24 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Constipation | 14.83 scores on a scale | Standard Deviation 24.3 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Fatigue | 10.24 scores on a scale | Standard Deviation 24.3 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | Baseline, Diarrhoea | 8.74 scores on a scale | Standard Deviation 21.07 |
| Rituximab + Bendamustine | Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population | CFB at EOT, Loss of Appetite | 9.36 scores on a scale | Standard Deviation 31.98 |
Secondary
DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
DCR was defined as the percentage of participants with a CR, PR, or SD based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or PD (any new lesion or an increase by ≥50% of previously involved sites from nadir).
Time frame: up to 77 months
Population: Natural Killer Cell Count-Low Full Analysis Set. A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafasitamab + Bendamustine | DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 75.0 percentage of participants |
| Rituximab + Bendamustine | DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 70.3 percentage of participants |
95% CI: [0.755, 3.457]
Secondary
Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD) based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or progressive disease (PD; any new lesion or an increase by ≥50% of previously involved sites from nadir).
Time frame: up to 77 months
Population: Full Analysis Set. A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafasitamab + Bendamustine | Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 76.1 percentage of participants |
| Rituximab + Bendamustine | Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 71.8 percentage of participants |
95% CI: [0.829, 1.985]
Secondary
Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Time frame: up to 44.7 months
Population: Natural Killer Cell Count-Low Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley. Only participants with CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 6.70 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 10.30 months |
95% CI: [0.673, 2.035]
Secondary
Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Time frame: up to 40.2 months
Population: Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley. Only participants with CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 7.40 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 12.10 months |
95% CI: [0.938, 1.745]
Secondary
Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup
Overall survival was defined as the time (in months) from randomization until death from any cause.
Time frame: up to 50.6 months
Population: Natural Killer Cell Count-Low Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup | 10.60 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup | 12.50 months |
95% CI: [0.682, 1.626]
Secondary
Kaplan-Meier Estimate of Overall Survival in the Overall Population
Overall survival was defined as the time (in months) from randomization until death from any cause.
Time frame: up to 50.0 months
Population: Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Overall Survival in the Overall Population | 14.60 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Overall Survival in the Overall Population | 20.20 months |
95% CI: [0.875, 1.452]
Secondary
Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup
Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first.
Time frame: up to 70.1 months
Population: Natural Killer Cell Count-Low Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup | 7.20 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup | 6.30 months |
95% CI: [0.57, 1.22]
Secondary
Kaplan-Meier Estimate of Time to Next Treatment in the Overall Population
Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first.
Time frame: up to 59.4 months
Population: Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Time to Next Treatment in the Overall Population | 8.80 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Time to Next Treatment in the Overall Population | 8.70 months |
95% CI: [0.794, 1.244]
Secondary
Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation.
Time frame: up to 40.6 months
Population: Natural Killer Cell Count-Low Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley. Only participants with progression/death as a result of lymphoma were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 8.00 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup | 10.00 months |
95% CI: [0.633, 1.595]
Secondary
Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation.
Time frame: up to 25.8 months
Population: Full Analysis Set. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley. Only participants with progression/death as a result of lymphoma were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tafasitamab + Bendamustine | Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 8.20 months |
| Rituximab + Bendamustine | Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Overall Population | 11.10 months |
95% CI: [0.831, 1.416]
Secondary
Number of Participants With Any Grade 3 or Higher TEAE
AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (or higher). Grade 1: mild; asymptomatic or mild symptoms. Grade 2: moderate. Grade 3: severe or medically significant but not immediately life threatening. Grade 4: life-threatening consequences. Grade 5: death. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
Time frame: up to 77 months
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafasitamab + Bendamustine | Number of Participants With Any Grade 3 or Higher TEAE | 191 participants |
| Rituximab + Bendamustine | Number of Participants With Any Grade 3 or Higher TEAE | 159 participants |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event was defined as any untoward medical occurrence in a participant administered a medicinal product, which did not necessarily have a causal relationship to this treatment. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it was considered related to that study drug. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
Time frame: up to 77 months
Population: Safety Analysis Set: all participants who received at least one dose of tafasitamab, bendamustine, or rituximab. Analyses were based on the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tafasitamab + Bendamustine | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 215 participants |
| Rituximab + Bendamustine | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 215 participants |
Secondary
Tafasitamab Serum Concentrations
Blood samples were collected for the assessment of serum concentrations of tafasitamab.
Time frame: pre-dose: Cycle 1 Days 1, 2, 3, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15, Cycles 4, 5, 6, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 Day 1. 1 hour post-dose: Cycle 1 Days 1, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15
Population: Pharmacokinetic (PK) Analysis Set: all participants who received at least one dose of tafasitamab and had at least one quantifiable serum tafasitamab concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 3 Day 15, 1 hour post-dose | 5.54 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30.1 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 4 Day 1, pre-dose | 3.27 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 43.2 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 5 Day 1, pre-dose | 1.95 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 54.6 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 6 Day 1, pre-dose | 1.60 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 61.2 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 7 Day 1, pre-dose | 1.14 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 75.3 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 1, pre-dose | 0.00 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 58.8 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 1, 1 hour post-dose | 2.45 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 37.1 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 2, pre-dose | 2.06 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30.2 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 3, pre-dose | 1.63 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30.4 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 4, pre-dose | 1.34 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 33.5 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 4, 1 hour post-dose | 3.84 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 31.8 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 15, pre-dose | 2.14 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 39.1 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 1 Day 15, 1 hour post-dose | 4.68 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 31.9 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 2 Day 1, pre-dose | 2.37 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 55.1 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 2 Day 1, 1 hour post-dose | 4.80 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 32.8 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 2 Day 15, pre-dose | 2.73 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 42.4 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 2 Day 15, 1 hour post-dose | 5.20 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 44.4 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 3 Day 1, pre-dose | 2.92 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 43.5 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 3 Day 1, 1 hour post-dose | 5.38 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 32.2 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 3 Day 15, pre-dose | 3.14 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 38.3 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 9 Day 1, pre-dose | 1.79 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 50.3 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 11 Day 1, pre-dose | 1.73 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 58.1 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 13 Day 1, pre-dose | 1.81 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 66.4 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 15 Day 1, pre-dose | 1.83 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 55.8 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 17 Day 1, pre-dose | 1.86 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 48.3 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 19 Day 1, pre-dose | 1.98 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 36.4 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 21 Day 1, pre-dose | 1.91 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 52 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 23 Day 1, pre-dose | 1.88 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 55.2 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 25 Day 1, pre-dose | 2.24 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 37.7 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 27 Day 1, pre-dose | 1.92 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 12.6 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 29 Day 1, pre-dose | 2.05 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 21.3 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 31 Day 1, pre-dose | 1.64 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 23.9 |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 33 Day 1, pre-dose | 1.45 micrograms per milliliter (µg/mL) | — |
| Tafasitamab + Bendamustine | Tafasitamab Serum Concentrations | Cycle 35 Day 1, pre-dose | 1.51 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 2.7 |