Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Brief summary
The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Detailed description
After completing the treatment period, all participants will be followed in the post-treatment follow-up period for up to 5 years. Thereafter, participants who received at least one dose of axicabtagene ciloleucel as protocol therapy will transition to a separate long term follow up (LTFU) study and complete the remainder of the 15-year follow-up assessments within KT-US-982-5968 (NCT05041309).
Interventions
BIOLOGICALAxicabtagene Ciloleucel
Administered intravenously
DRUGPlatinum-containing Salvage Chemotherapy
Platinum-containing salvage chemotherapy (Rituximab-ifosfamide, carboplatin, etoposide (R-ICE), Rituximab-dexamethasone, cytarabine, cisplatin,oxaliplatin (R-DHAP), Rituximab-etoposide, methylprednisolone, cisplatin, cytarabine (R-ESHAP), or Rituximab-gemcitabine, dexamethasone, cisplatin/carboplatin (R-GDP) as selected by treating investigator).
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
Sponsors
Kite, A Gilead Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically proven large B-cell lymphoma (BCL) including the following types defined by World Health Organization (WHO) 2016. * Diffuse large B-cell lymphoma (DLBCL) not otherwise specified activated B-cell/ germinal center B-cell (ABC/GCB). * High-grade B-cell lymphoma (HGBL) with or without myelocytomatosis oncogene (MYC) and BCL 2 and/or BCL 6 rearrangement. * DLBCL arising from follicular lymphoma (FL). * T-cell/histiocyte rich large B-cell lymphoma. * DLBCL associated with chronic inflammation. * Primary cutaneous DLBCL, leg type. * Epstein-Barr virus (EBV) + DLBCL. * Relapsed or refractory disease after first-line chemoimmunotherapy. * Refractory disease defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded. * Progressive disease (PD) as best response to first-line therapy. * Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP). * Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy. * Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of first-line therapy. * Individuals must have received adequate first-line therapy including at a minimum: * Anti-Cluster of Differentiation 20 antigen (CD20) monoclonal antibody unless investigator determines that tumor is CD20 negative, and * An anthracycline containing chemotherapy regimen. * No known history or suspicion of central nervous system involvement by lymphoma. * Eastern cooperative oncology group (ECOG) performance status of 0 or 1. * Adequate bone marrow function as evidenced by: * Absolute neutrophil count (ANC) ≥ 1000/μl * Platelet ≥ 75,000/μl * Absolute lymphocyte count ≥ 100/μl * Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by: * Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min. * Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN). * Total bilirubin ≤ 1.5 mg/dl * Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an Echocardiogram (ECHO), and no clinically significant Electrocardiogram (ECG) findings. * No clinically significant pleural effusion. * Baseline oxygen saturation \> 92% on room air. Key
Exclusion criteria
* History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years. * Received more than one line of therapy for DLBCL. * History of autologous or allogeneic stem cell transplant. * Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management. * Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or anti-hepatitis C virus (HCV) positive. If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing. * Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases. * History or presence of non-malignant central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. * Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted. * History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment. * History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment. * History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years. * History of anti-Cluster of Differentiation 19 (CD19) or chimeric antigen receptor (CAR)-T therapy or history of prior randomization in ZUMA-7. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival (EFS) Per Blinded Central Assessment | From randomization date up to a median follow-up: 24.9 months | EFS:Time from randomization to disease progression (PD), best response of stable disease (SD) up to Day 150, start of new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD=Score 4 (uptake moderately \> liver) or 5 (uptake markedly \> liver and/or new lesions) with increased uptake from baseline; New fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma rather than another etiology or in bone marrow; Individual node/lesion abnormal with longest diameter \> 1.5 cm, ≥ 50% increase from nadir; Splenic length increase \> 50% of prior increase beyond baseline or ≥ 2 cm increase if no prior splenomegaly; New/recurrent splenomegaly, progression of non-measurable lesions, new lesion, or new/recurrent bone marrow involvement. KM estimates was used for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 74.9 months | Overall survival is defined as the time from randomization to death from any cause. Kaplan-Meier (KM) estimates were used for analysis. |
| Duration of Response (DOR) Per Blinded Central Assessments | From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (Up to 37.8 months) | DOR was defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and was the time from the first objective response per Lugano classification to disease progression or death from any cause. Objective response was defined in outcome measure 2 and disease progression was defined in outcome measure 1. KM estimates were used for analysis. |
| Modified Event Free Survival (mEFS) Per Blinded Central Assessment | From randomization date up to a median follow-up: 24.9 months | Modified event free survival is defined the same way as EFS, except that a best response of SD up to and including Day 150 assessment post randomization was not considered an event. KM estimates were used for analysis. |
| EFS Per Investigator Disease Assessments | From randomization date up to a median follow-up: 47.2 months | EFS was defined as the time from randomization to the earliest date of disease progression per the Lugano Classification, best response of stable disease (SD) up to and including Day 150, commencement of new lymphoma therapy, or death from any cause. Disease progression is defined in outcome measure 1. |
| Progression-Free Survival (PFS) Per Investigator Disease Assessments | From randomization date up to a median follow-up: 47.2 months | PFS is defined as the time from the randomization date to the date of disease progression per Lugano classification or death from any cause. Disease progression is defined in outcome measure 1. KM estimates were used for analysis. |
| Modified Event Free Survival (mEFS) Per Investigator Assessment | From randomization date up to a median follow-up: 47.2 months | mEFS is defined the same way as EFS, except that a best response of SD up to and including Day 150 assessment post randomization was not considered an event. KM estimates were used for analysis. |
| Change From Baseline in Global Health Status Scores | Baseline, Days 50, 100, and 150; Months 9, 12, 15, 18, 21 and 24 | Global health status was measured using European Organization for Research and Treatment of Cancer (EORTC) Quality Life Questionnaire (QLQ) C-30. This health related quality of life (HRQoL) questionnaire was comprised of 15 questions on functional scales, 13 questions on symptom scales and 2 on global health status scale. Global Health Status used a 7 point Likert-type scale of 1 (Very poor) to 7 (Excellent). All scores were transformed to 0-100. Higher scores for Global Health Status indicated better HRQoL. |
| Objective Response Rate (ORR) Per Blinded Central Assessment | From randomization date up to a median follow-up: 24.9 months | ORR: Percentage of participants with CR (Complete Metabolic Response (CMR);Complete Radiologic Response (CRR)) or PR (partial metabolic response (PMR); partial radiologic response (PRR)).CMR: Positron emission tomography (PET) 5-point scale scores: 1-No uptake above background; 2-Uptake ≤mediastinum; 3-Uptake \>mediastinum but ≤liver, with/without residual mass; no new lesions, no FDG-avid disease in bone marrow. CRR: Target nodes/nodal masses regressed ≤1.5 cm in longest diameter, no extralymphatic sites, no non-measured lesions, normal organ size, no new sites, normal bone marrow morphology. PMR: Scores 4 (uptake moderately \>liver), 5 (uptake markedly \>liver, new lesions) with reduced uptake from baseline and residual mass, no new lesions. Responding at interim/residual disease at end of treatment. PRR: ≥50% decrease in sum of diameters of up to 6 target measurable lesions, no increase in non-measured lesions, spleen length decreased \>50% if previously enlarged, no new lesion sites. |
| Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Baseline, Days 50, 100, 150; Months 9, 12, 15, 18, 21 and 24 | The Euro-QOL (EQ) Five Dimensions (5D) Five Levels (5L), EQ-5D-5L questionnaire was a generic measure of health status that provided a simple descriptive profile and a single index value. The EQ-5D-5L comprised 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health stated using a visual analog scale (VAS). The total score for EQ-5D-5L index was presented on a range from 0 to 1 where higher scores indicated better outcome. A positive change from Baseline indicates improvement. |
| Change From Baseline in EQ-5D-5L VAS Scale Score | Baseline, Days 50, 100, 150; Months 9, 12, 15, 18, 21 and 24 | The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the participants' health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each participant for his or her current HRQoL state and scored 0 (the worst health you can imagine) to 100 (the best health you can imagine). The value 100 indicates improvement. |
| Number of Participants With Post-dose Anti-Axicabtagene Ciloleucel Antibodies | Up to 74.9 months | — |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | From first dose up to 61.8 months | A TEAE was defined as any AE that begins on or after the first dose of study treatment (axicabtagene ciloleucel infusion or SOC), excluding bridging therapy. |
| Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | From first dose up to 61.8 months | Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Percentages were rounded off. |
| Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | From first dose up to 61.8 months | Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Percentages were rounded off. |
| Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Baseline, Days 50, 100, 150, Months 9, 12, 15, 18, 21 and 24 | The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants were asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 7 (excellent). The 5 scores were transformed to a scale from 0 to 100, where a high score indicated better QoL. A positive change from baseline indicates better QoL. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Middle East, Europe, and Australia.
Pre-assignment details
437 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Axicabtagene Ciloleucel Participants received cyclophosphamide 500 mg/m\^2/day IV infusion and fludarabine 30 mg/m\^2/day IV infusion conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-CD 19 CAR transduced autologous T cells/kg on Day 0. | 180 |
| Standard of Care Therapy Participants received 2 or 3, 21-day cycles of second-line chemotherapy regimen:
* R-ICE: rituximab 375mg/m\^2 before chemotherapy, ifosfamide 5g/m\^2 24 hours CI on Day 2 + mesna, carboplatin AUC 5 Day 2, maximum dose 800mg, etoposide 100mg/m\^2/day on Days 1-3;
* R-ESHAP: rituximab 375mg/m\^2 Day 1, etoposide 40mg/m\^2/day IV on Days 1-4, methylprednisolone 500mg/day IV on Days 1-4 or 5, cisplatin at 25mg/m\^2/day CI Days 1-4, cytarabine 2g/m\^2 on Day 5;
* R-GDP: rituximab 375mg/m\^2 Day 1 (or Day 8), gemcitabine 1g/m\^2 on Days 1 and 8, dexamethasone 40mg on Days 1-4, cisplatin 75mg/m\^2 Day 1 or carboplatin AUC=5; or
* R-DHAP: rituximab 375mg/m\^2 before chemotherapy, dexamethasone 40mg/day on Days 1-4, high dose cytarabine 2g/m\^2 every 12 hours for 2 doses on Day 2 following platinum, cisplatin 100mg/m\^2 24 hours CI on Day 1 or oxaliplatin 100mg/m\^2.
Participants who responded to second-line chemotherapy got high dose therapy and autologous stem cell transplant. | 179 |
| Total | 359 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 84 | 91 |
| Overall Study | Investigator Decision | 0 | 1 |
| Overall Study | Lost to Follow-up | 9 | 5 |
| Overall Study | Reason Not Specified | 2 | 2 |
| Overall Study | Rollover to Long-term Follow-up Study Criteria | 80 | 0 |
| Overall Study | Subject Withdrawal of Consent from Further Follow-up | 3 | 13 |
Baseline characteristics
| Characteristic | Axicabtagene Ciloleucel | Total | Standard of Care Therapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 109 Participants | 58 Participants |
| Age, Categorical Between 18 and 65 years | 129 Participants | 250 Participants | 121 Participants |
| Age, Continuous | 57.1 years STANDARD_DEVIATION 12 | 57.2 years STANDARD_DEVIATION 12.1 | 57.4 years STANDARD_DEVIATION 12.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 18 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 167 Participants | 336 Participants | 169 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 22 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 18 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 145 Participants | 297 Participants | 152 Participants |
| Region of Enrollment Australia | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment Austria | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Belgium | 4 Participants | 7 Participants | 3 Participants |
| Region of Enrollment Canada | 10 Participants | 20 Participants | 10 Participants |
| Region of Enrollment France | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment Germany | 1 Participants | 6 Participants | 5 Participants |
| Region of Enrollment Israel | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment Italy | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Netherlands | 11 Participants | 25 Participants | 14 Participants |
| Region of Enrollment Spain | 6 Participants | 15 Participants | 9 Participants |
| Region of Enrollment Sweden | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Switzerland | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 4 Participants | 12 Participants | 8 Participants |
| Region of Enrollment United States | 130 Participants | 250 Participants | 120 Participants |
| Sex: Female, Male Female | 70 Participants | 122 Participants | 52 Participants |
| Sex: Female, Male Male | 110 Participants | 237 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 81 / 180 | 101 / 179 | 3 / 10 |
| other Total, other adverse events | 170 / 170 | 166 / 168 | 10 / 10 |
| serious Total, serious adverse events | 96 / 170 | 78 / 168 | 2 / 10 |
Outcome results
Primary
Event Free Survival (EFS) Per Blinded Central Assessment
EFS:Time from randomization to disease progression (PD), best response of stable disease (SD) up to Day 150, start of new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD=Score 4 (uptake moderately \> liver) or 5 (uptake markedly \> liver and/or new lesions) with increased uptake from baseline; New fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma rather than another etiology or in bone marrow; Individual node/lesion abnormal with longest diameter \> 1.5 cm, ≥ 50% increase from nadir; Splenic length increase \> 50% of prior increase beyond baseline or ≥ 2 cm increase if no prior splenomegaly; New/recurrent splenomegaly, progression of non-measurable lesions, new lesion, or new/recurrent bone marrow involvement. KM estimates was used for analysis.
Time frame: From randomization date up to a median follow-up: 24.9 months
Population: Participants in Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | Event Free Survival (EFS) Per Blinded Central Assessment | 8.3 months |
| Standard of Care Therapy | Event Free Survival (EFS) Per Blinded Central Assessment | 2.0 months |
p-value: <0.000195% CI: [0.308, 0.514]Log Rank
Secondary
Change From Baseline in EORTC QLQ-C30 Physical Functioning Score
The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants were asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 7 (excellent). The 5 scores were transformed to a scale from 0 to 100, where a high score indicated better QoL. A positive change from baseline indicates better QoL.
Time frame: Baseline, Days 50, 100, 150, Months 9, 12, 15, 18, 21 and 24
Population: Participants in QoL analysis set with data available at given timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Score at Baseline | 83.5 Score on scale | Standard Deviation 17.7 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Day 50 | -12.9 Score on scale | Standard Deviation 21.7 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Day 100 | -1.8 Score on scale | Standard Deviation 17.8 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Day 150 | 1.3 Score on scale | Standard Deviation 18.9 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 9 | 4.1 Score on scale | Standard Deviation 17.1 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 12 | 3.4 Score on scale | Standard Deviation 20.8 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 15 | 3.9 Score on scale | Standard Deviation 19.3 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 18 | 5.0 Score on scale | Standard Deviation 15.1 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 21 | 6.0 Score on scale | Standard Deviation 16.1 |
| Axicabtagene Ciloleucel | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 24 | 3.7 Score on scale | Standard Deviation 16.5 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 18 | 3.2 Score on scale | Standard Deviation 17.9 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Score at Baseline | 85.3 Score on scale | Standard Deviation 18.9 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 12 | 0.4 Score on scale | Standard Deviation 20.3 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Day 50 | -8.3 Score on scale | Standard Deviation 17.5 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 24 | 5.6 Score on scale | Standard Deviation 8 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Day 100 | -15.0 Score on scale | Standard Deviation 19.1 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 15 | 1.6 Score on scale | Standard Deviation 16.1 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Day 150 | -5.2 Score on scale | Standard Deviation 21.3 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 21 | 4.3 Score on scale | Standard Deviation 21.4 |
| Standard of Care Therapy | Change From Baseline in EORTC QLQ-C30 Physical Functioning Score | Change from Baseline at Study Month 9 | -2.4 Score on scale | Standard Deviation 23.5 |
Comparison: Difference in mean change of scores from Baseline at Day 100.p-value: <0.000195% CI: [8, 18.2]Mixed Model with Repeated Measures
Comparison: Difference in mean change of scores from Baseline at Day 150.p-value: 0.125395% CI: [-0.9, 11]Mixed Model with Repeated Measures
Secondary
Change From Baseline in EQ-5D-5L VAS Scale Score
The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the participants' health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each participant for his or her current HRQoL state and scored 0 (the worst health you can imagine) to 100 (the best health you can imagine). The value 100 indicates improvement.
Time frame: Baseline, Days 50, 100, 150; Months 9, 12, 15, 18, 21 and 24
Population: Participants in QoL analysis set with data available at given timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Score at Baseline | 72.4 Score on scale | Standard Deviation 18.7 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Day 50 | -1.9 Score on scale | Standard Deviation 18.7 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Day 100 | 4.0 Score on scale | Standard Deviation 18.4 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Day 150 | 9.1 Score on scale | Standard Deviation 19.4 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 9 | 11.4 Score on scale | Standard Deviation 19.9 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 12 | 10.1 Score on scale | Standard Deviation 19.9 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 15 | 10.7 Score on scale | Standard Deviation 20.7 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 18 | 15.1 Score on scale | Standard Deviation 17.1 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 21 | 14.0 Score on scale | Standard Deviation 17.2 |
| Axicabtagene Ciloleucel | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 24 | 10.9 Score on scale | Standard Deviation 18.8 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 18 | 9.3 Score on scale | Standard Deviation 13.6 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Score at Baseline | 74.4 Score on scale | Standard Deviation 20.1 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 12 | 6.6 Score on scale | Standard Deviation 17.8 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Day 50 | -4.4 Score on scale | Standard Deviation 16.7 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 24 | 12.2 Score on scale | Standard Deviation 15.3 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Day 100 | -8.2 Score on scale | Standard Deviation 19.8 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 15 | 8.2 Score on scale | Standard Deviation 13.7 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Day 150 | -2.2 Score on scale | Standard Deviation 22.2 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 21 | 10.1 Score on scale | Standard Deviation 14.3 |
| Standard of Care Therapy | Change From Baseline in EQ-5D-5L VAS Scale Score | Change from Baseline at Study Month 9 | 4.4 Score on scale | Standard Deviation 19 |
Comparison: Difference in mean change of scores from Baseline at Day 100.p-value: <0.000195% CI: [8.5, 18.8]Mixed Model with Repeated Measures
Comparison: Difference in mean change of scores from Baseline at Day 150.p-value: 0.000495% CI: [5.4, 17.1]Mixed Model with Repeated Measures
Comparison: Difference in mean change of scores from Baseline at Month 9.p-value: 0.254995% CI: [-2.3, 10]Mixed Model with Repeated Measures
Secondary
Change From Baseline in Global Health Status Scores
Global health status was measured using European Organization for Research and Treatment of Cancer (EORTC) Quality Life Questionnaire (QLQ) C-30. This health related quality of life (HRQoL) questionnaire was comprised of 15 questions on functional scales, 13 questions on symptom scales and 2 on global health status scale. Global Health Status used a 7 point Likert-type scale of 1 (Very poor) to 7 (Excellent). All scores were transformed to 0-100. Higher scores for Global Health Status indicated better HRQoL.
Time frame: Baseline, Days 50, 100, and 150; Months 9, 12, 15, 18, 21 and 24
Population: Participants in Quality of Life (QoL) Analysis Set with data available at given timepoint were analyzed. The QoL Analysis Set was defined as the subset of participants in the Full Analysis Set who have a baseline and Day 150 post-randomization QoL assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Score at Baseline | 68.6 Score on scale | Standard Deviation 19.9 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Day 50 | -7.4 Score on scale | Standard Deviation 20.2 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Day 100 | 1.3 Score on scale | Standard Deviation 19.6 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Day 150 | 5.9 Score on scale | Standard Deviation 24.9 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 9 | 8.0 Score on scale | Standard Deviation 22.7 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 12 | 8.6 Score on scale | Standard Deviation 24.9 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 15 | 9.0 Score on scale | Standard Deviation 22.3 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 18 | 10.2 Score on scale | Standard Deviation 20.9 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 21 | 10.0 Score on scale | Standard Deviation 21.5 |
| Axicabtagene Ciloleucel | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 24 | 8.6 Score on scale | Standard Deviation 21 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 18 | 6.5 Score on scale | Standard Deviation 21.3 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Score at Baseline | 70.1 Score on scale | Standard Deviation 23.1 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 12 | 9.1 Score on scale | Standard Deviation 20.2 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Day 50 | -8.5 Score on scale | Standard Deviation 22.7 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 24 | 13.2 Score on scale | Standard Deviation 17.2 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Day 100 | -15.3 Score on scale | Standard Deviation 22.7 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 15 | 9.9 Score on scale | Standard Deviation 18.9 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Day 150 | -4.2 Score on scale | Standard Deviation 23.7 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 21 | 15.0 Score on scale | Standard Deviation 19.6 |
| Standard of Care Therapy | Change From Baseline in Global Health Status Scores | Change from Baseline at Study Month 9 | 3.5 Score on scale | Standard Deviation 23.7 |
Comparison: Difference in mean change of scores from Baseline at Day 100.p-value: <0.000195% CI: [12.3, 23.9]Mixed Model with Repeated Measures
Comparison: Difference in mean change of scores from Baseline at Day 150.p-value: 0.012495% CI: [2.6, 17]Mixed Model with Repeated Measures
Comparison: Difference in mean change of scores from Baseline at Month 9.p-value: 0.265595% CI: [-3.3, 12]Mixed Model with Repeated Measures
Secondary
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score
The Euro-QOL (EQ) Five Dimensions (5D) Five Levels (5L), EQ-5D-5L questionnaire was a generic measure of health status that provided a simple descriptive profile and a single index value. The EQ-5D-5L comprised 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health stated using a visual analog scale (VAS). The total score for EQ-5D-5L index was presented on a range from 0 to 1 where higher scores indicated better outcome. A positive change from Baseline indicates improvement.
Time frame: Baseline, Days 50, 100, 150; Months 9, 12, 15, 18, 21 and 24
Population: Participants in QoL analysis set with data available at given timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Score at Baseline | 0.803 Score on scale | Standard Deviation 0.21 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Day 50 | -0.049 Score on scale | Standard Deviation 0.205 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Day 100 | 0.012 Score on scale | Standard Deviation 0.191 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Day 150 | 0.050 Score on scale | Standard Deviation 0.212 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 9 | 0.064 Score on scale | Standard Deviation 0.19 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 12 | 0.072 Score on scale | Standard Deviation 0.241 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 15 | 0.051 Score on scale | Standard Deviation 0.209 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 18 | 0.094 Score on scale | Standard Deviation 0.18 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 21 | 0.089 Score on scale | Standard Deviation 0.235 |
| Axicabtagene Ciloleucel | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 24 | 0.051 Score on scale | Standard Deviation 0.239 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 18 | 0.072 Score on scale | Standard Deviation 0.188 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Score at Baseline | 0.799 Score on scale | Standard Deviation 0.25 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 12 | 0.051 Score on scale | Standard Deviation 0.2 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Day 50 | -0.003 Score on scale | Standard Deviation 0.198 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 24 | 0.117 Score on scale | Standard Deviation 0.138 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Day 100 | -0.068 Score on scale | Standard Deviation 0.246 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 15 | 0.080 Score on scale | Standard Deviation 0.125 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Day 150 | 0.014 Score on scale | Standard Deviation 0.208 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 21 | 0.110 Score on scale | Standard Deviation 0.177 |
| Standard of Care Therapy | Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale Index Score | Change from Baseline at Study Month 9 | 0.015 Score on scale | Standard Deviation 0.197 |
Comparison: Difference in mean change of scores from Baseline at Day 100.p-value: 0.011295% CI: [0.024, 0.138]Mixed Model with Repeated Measures
Comparison: Difference in mean change of scores from Baseline at Day 150.p-value: 0.370395% CI: [-0.034, 0.091]Mixed Model with Repeated Measures
Secondary
Duration of Response (DOR) Per Blinded Central Assessments
DOR was defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and was the time from the first objective response per Lugano classification to disease progression or death from any cause. Objective response was defined in outcome measure 2 and disease progression was defined in outcome measure 1. KM estimates were used for analysis.
Time frame: From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (Up to 37.8 months)
Population: Participants in the Full Analysis Set with objective response were analyzed. Participants not meeting the criteria by the analysis data cut-off date were censored at their last evaluable disease assessment date prior to the data cut-off date or new lymphoma therapy start date (including stem cell transplant in the axicabtagene ciloleucel arm or retreatment of axicabtagene ciloleucel), whichever was earlier.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | Duration of Response (DOR) Per Blinded Central Assessments | 26.9 months |
| Standard of Care Therapy | Duration of Response (DOR) Per Blinded Central Assessments | 8.9 months |
p-value: 0.069595% CI: [0.488, 1.108]Log Rank
Secondary
EFS Per Investigator Disease Assessments
EFS was defined as the time from randomization to the earliest date of disease progression per the Lugano Classification, best response of stable disease (SD) up to and including Day 150, commencement of new lymphoma therapy, or death from any cause. Disease progression is defined in outcome measure 1.
Time frame: From randomization date up to a median follow-up: 47.2 months
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | EFS Per Investigator Disease Assessments | 10.8 months |
| Standard of Care Therapy | EFS Per Investigator Disease Assessments | 2.3 months |
95% CI: [0.327, 0.545]
Secondary
Modified Event Free Survival (mEFS) Per Blinded Central Assessment
Modified event free survival is defined the same way as EFS, except that a best response of SD up to and including Day 150 assessment post randomization was not considered an event. KM estimates were used for analysis.
Time frame: From randomization date up to a median follow-up: 24.9 months
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | Modified Event Free Survival (mEFS) Per Blinded Central Assessment | 10.3 months |
| Standard of Care Therapy | Modified Event Free Survival (mEFS) Per Blinded Central Assessment | 2.0 months |
p-value: <0.000195% CI: [0.29, 0.487]Log Rank
Secondary
Modified Event Free Survival (mEFS) Per Investigator Assessment
mEFS is defined the same way as EFS, except that a best response of SD up to and including Day 150 assessment post randomization was not considered an event. KM estimates were used for analysis.
Time frame: From randomization date up to a median follow-up: 47.2 months
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | Modified Event Free Survival (mEFS) Per Investigator Assessment | 12.6 months |
| Standard of Care Therapy | Modified Event Free Survival (mEFS) Per Investigator Assessment | 2.3 months |
95% CI: [0.318, 0.532]
Secondary
Number of Participants With Post-dose Anti-Axicabtagene Ciloleucel Antibodies
Time frame: Up to 74.9 months
Population: Participants in the Safety Analysis Set were analyzed. The Safety Analysis Set was defined as the subset of all randomized participants who received at least 1 dose of axicabtagene ciloleucel as protocol therapy or SOC chemotherapy as protocol therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Axicabtagene Ciloleucel | Number of Participants With Post-dose Anti-Axicabtagene Ciloleucel Antibodies | 0 Participants |
Secondary
Objective Response Rate (ORR) Per Blinded Central Assessment
ORR: Percentage of participants with CR (Complete Metabolic Response (CMR);Complete Radiologic Response (CRR)) or PR (partial metabolic response (PMR); partial radiologic response (PRR)).CMR: Positron emission tomography (PET) 5-point scale scores: 1-No uptake above background; 2-Uptake ≤mediastinum; 3-Uptake \>mediastinum but ≤liver, with/without residual mass; no new lesions, no FDG-avid disease in bone marrow. CRR: Target nodes/nodal masses regressed ≤1.5 cm in longest diameter, no extralymphatic sites, no non-measured lesions, normal organ size, no new sites, normal bone marrow morphology. PMR: Scores 4 (uptake moderately \>liver), 5 (uptake markedly \>liver, new lesions) with reduced uptake from baseline and residual mass, no new lesions. Responding at interim/residual disease at end of treatment. PRR: ≥50% decrease in sum of diameters of up to 6 target measurable lesions, no increase in non-measured lesions, spleen length decreased \>50% if previously enlarged, no new lesion sites.
Time frame: From randomization date up to a median follow-up: 24.9 months
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axicabtagene Ciloleucel | Objective Response Rate (ORR) Per Blinded Central Assessment | 83 percentage of participants |
| Standard of Care Therapy | Objective Response Rate (ORR) Per Blinded Central Assessment | 50 percentage of participants |
p-value: <0.000195% CI: [23.2, 42.1]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
Overall survival is defined as the time from randomization to death from any cause. Kaplan-Meier (KM) estimates were used for analysis.
Time frame: Up to 74.9 months
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | Overall Survival (OS) | NA months |
| Standard of Care Therapy | Overall Survival (OS) | 35.1 months |
p-value: 0.02795% CI: [0.53, 1.007]Log Rank
Secondary
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as any AE that begins on or after the first dose of study treatment (axicabtagene ciloleucel infusion or SOC), excluding bridging therapy.
Time frame: From first dose up to 61.8 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axicabtagene Ciloleucel | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
Secondary
Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher
Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Percentages were rounded off.
Time frame: From first dose up to 61.8 months
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Leukocytes (10^9/L) | 95 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Calcium (mmol/L) | 8 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Neutrophils (10^9/L) | 94 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Glucose (mmol/L) | 0 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Hemoglobin (mmol/L) | 41 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Magnesium (mmol/L) | 2 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Platelets (10^9/L) | 26 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Phosphate (mmol/L) | 5 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Lymphocytes (10^9/L) | 99 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Potassium (mmol/L) | 6 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Albumin (g/L) | 4 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Sodium (mmol/L) | 12 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Sodium (mmol/L) | 2 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Hemoglobin (mmol/L) | 44 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Leukocytes (10^9/L) | 56 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Lymphocytes (10^9/L) | 68 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Neutrophils (10^9/L) | 51 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Platelets (10^9/L) | 63 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Albumin (g/L) | 1 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Calcium (mmol/L) | 2 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Glucose (mmol/L) | 0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Magnesium (mmol/L) | 3 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Phosphate (mmol/L) | 5 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher | Potassium (mmol/L) | 7 percentage of participants |
Secondary
Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher
Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Percentages were rounded off.
Time frame: From first dose up to 61.8 months
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Lymphocytes (10^9/L) | 0 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Calcium (mmol/L) | 2 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Alkaline Phosphatase (U/L) | 1 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Creatinine (umol/L) | 4 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Leukocytes (10^9/L) | 0 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Glucose (mmol/L) | 14 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Aspartate Aminotransferase (U/L) | 6 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Magnesium (mmol/L) | 2 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Alanine Aminotransferase (U/L) | 6 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Potassium (mmol/L) | 0 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Bilirubin (umol/L) | 2 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Sodium (mmol/L) | 0 percentage of participants |
| Axicabtagene Ciloleucel | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Hemoglobin (mmol/L) | 0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Sodium (mmol/L) | 0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Hemoglobin (mmol/L) | 0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Leukocytes (10^9/L) | 1 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Lymphocytes (10^9/L) | 0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Alanine Aminotransferase (U/L) | 4 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Alkaline Phosphatase (U/L) | 1 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Aspartate Aminotransferase (U/L) | 2 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Bilirubin (umol/L) | 1 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Calcium (mmol/L) | 1 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Creatinine (umol/L) | 1 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Glucose (mmol/L) | 5 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Magnesium (mmol/L) | 0 percentage of participants |
| Standard of Care Therapy | Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher | Potassium (mmol/L) | 1 percentage of participants |
Secondary
Progression-Free Survival (PFS) Per Investigator Disease Assessments
PFS is defined as the time from the randomization date to the date of disease progression per Lugano classification or death from any cause. Disease progression is defined in outcome measure 1. KM estimates were used for analysis.
Time frame: From randomization date up to a median follow-up: 47.2 months
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axicabtagene Ciloleucel | Progression-Free Survival (PFS) Per Investigator Disease Assessments | 14.7 months |
| Standard of Care Therapy | Progression-Free Survival (PFS) Per Investigator Disease Assessments | 3.7 months |
95% CI: [0.383, 0.669]