Trial Outcomes & Findings for Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma (NCT NCT03391466)

Last Updated: 2024-12-24

Results Overview

EFS:Time from randomization to disease progression (PD), best response of SD up to and including Day 150, commencement of subsequent new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD=score 4 (uptake moderately\>liver)/5 (uptake markedly \>liver and/or new lesions) with an increase in intensity of uptake from baseline;new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma at interim/EOT assessment, rather than another etiology or in bone marrow;an individual node/lesion must be abnormal with LDi \>1.5 cm, increase by ≥50% from cross-product of LDi and perpendicular diameter nadir, increase in LDi or shortest axis perpendicular to LDi from nadir, splenic length must increase by \>50% of extent of its prior increase beyond Baseline. If no prior splenomegaly, increase must be ≥2 cm from baseline;new/recurrent splenomegaly;new/clear progression of pre-existing NMLs;new lesion;new/recurrent bone marrow involvement. KM estimates was used for analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

359 participants

Primary outcome timeframe

From randomization date up to a median follow-up: 24.9 months

Results posted on

2024-12-24

Participant Flow

Participants were enrolled at study sites in the North America, Middle East, Europe, and Australia. The data for participant flow and adverse events are reported up to data cut-off date: 25 January 2023. The data reported for outcome measures 1-13 are complete as per the pre-specified planned analysis in the protocol.

437 participants were screened.

Participant milestones

Participant milestones
Measure	Axicabtagene Ciloleucel Participants received cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV 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-CD19 CAR transduced autologous T cells/kg on Day 0.	Standard of Care Therapy Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who will respond will get high dose therapy and autologous stem cell transplant up to 60 months.
Overall Study STARTED	180	179
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	180	179

Reasons for withdrawal

Reasons for withdrawal
Measure	Axicabtagene Ciloleucel Participants received cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV 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-CD19 CAR transduced autologous T cells/kg on Day 0.	Standard of Care Therapy Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who will respond will get high dose therapy and autologous stem cell transplant up to 60 months.
Overall Study Death	82	85
Overall Study Still on study	93	74
Overall Study Subject withdrawal of consent from further follow-up	0	13
Overall Study Lost to Follow-up	5	5
Overall Study Investigator decision	0	1
Overall Study Other	0	1

Baseline Characteristics

Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received cyclophosphamide 500 mg/m\^2/day IV and fludarabine 30 mg/m\^2/day IV 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-CD19 CAR transduced autologous T cells/kg on Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.	Total n=359 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	129 Participants n=5 Participants	121 Participants n=7 Participants	250 Participants n=5 Participants
Age, Categorical >=65 years	51 Participants n=5 Participants	58 Participants n=7 Participants	109 Participants n=5 Participants
Age, Continuous	57 years STANDARD_DEVIATION 12.0 • n=5 Participants	57 years STANDARD_DEVIATION 12.2 • n=7 Participants	57 years STANDARD_DEVIATION 12.1 • n=5 Participants
Sex: Female, Male Female	70 Participants n=5 Participants	52 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Male	110 Participants n=5 Participants	127 Participants n=7 Participants	237 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	167 Participants n=5 Participants	169 Participants n=7 Participants	336 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	145 Participants n=5 Participants	152 Participants n=7 Participants	297 Participants n=5 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	130 Participants n=5 Participants	120 Participants n=7 Participants	250 Participants n=5 Participants
Region of Enrollment United Kingdom	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Switzerland	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Spain	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Canada	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment Belgium	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Netherlands	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Sweden	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Italy	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Israel	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment France	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Germany	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Austria	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization date up to a median follow-up: 24.9 months

Population: Participants in FAS were analyzed.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Event Free Survival (EFS) Per Blinded Central Assessment	8.3 months Interval 4.5 to 15.8	2.0 months Interval 1.6 to 2.8

SECONDARY outcome

Timeframe: From randomization date up to a median follow-up: 24.9 months

Population: Participants in FAS were analyzed.

ORR: Percentage of participants with CR \[CMR;CRR\] or PR \[partial metabolic response (PMR); partial radiologic response (PRR)\].CMR: PET 5PS scores of 1 (no uptake above background, 2(uptake≤mediastinum), 3(uptake\>mediastinum but≤liver) with/without a residual mass;no new lesions; no evidence of FDG-avid disease in BM. CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in LDi;no extralymphatic sites of disease;absent non-measured lesions (NMLs);organ enlargement regress to normal;no new sites;bone marrow morphology normal. PMR:scores 4 (uptake moderately\>liver),5(uptake markedly \> liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT).PRR: ≥50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by \>50% in length beyond normal;no new sites.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Objective Response Rate (ORR) Per Blinded Central Assessment	83 percentage of participants Interval 77.1 to 88.5	50 percentage of participants Interval 42.7 to 57.8

SECONDARY outcome

Timeframe: From randomization date up to a median follow-up: 47.2 months

Population: Participants in FAS were analyzed.

Overall survival is defined as the time from randomization to death from any cause. Kaplan-Meier (KM) estimates was used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Overall Survival (OS)	NA months Interval 28.6 to Median and upper limit of CI were not reached due to insufficient number of events.	31.1 months Interval 17.1 to Median and upper limit of CI were not reached due to insufficient number of events

SECONDARY outcome

Timeframe: 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 FAS with 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.

DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response per Lugano classification to disease progression or death from any cause. Objective response is defined in outcome measure 2 and disease progression is defined in outcome measure 1. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=150 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=90 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Duration of Response (DOR) Per Blinded Central Assessments	26.9 months Interval 13.6 to The upper limit of CI were not reached due to insufficient number of events.	8.9 months Interval 5.7 to The upper limit of CI were not reached due to insufficient number of events.

SECONDARY outcome

Timeframe: From randomization date up to a median follow-up: 24.9 months

Population: Participants in FAS were analyzed.

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.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Modified Event Free Survival (mEFS) Per Blinded Central Assessment	10.3 months Interval 5.0 to 21.5	2.0 months Interval 1.6 to 2.8

SECONDARY outcome

Timeframe: From randomization date up to a median follow-up: 47.2 months

Population: Participants in FAS were analyzed.

EFS was defined as the time from randomization to the earliest date of disease progression per the IWG 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.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Event Free Survival Per Investigator Disease Assessments	10.8 months Interval 5.0 to 25.5	2.3 months Interval 1.7 to 3.1

SECONDARY outcome

Timeframe: From randomization date up to a median follow-up: 47.2 months

Population: Participants in FAS were analyzed.

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 was used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Progression-Free Survival (PFS) Per Investigator Disease Assessments	14.7 months Interval 5.4 to 43.5	3.7 months Interval 2.9 to 5.3

SECONDARY outcome

Timeframe: From randomization date up to a median follow-up: 47.2 months

Population: Participants in FAS were analyzed.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=180 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=179 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Modified Event Free Survival (mEFS) Per Investigator Assessment	12.6 months Interval 5.0 to 29.1	2.3 months Interval 1.7 to 3.1

SECONDARY outcome

Timeframe: Baseline, Days 50, 100, and 150; Months 9, 12, 15, 18, 21 and 24

Population: The QoL analysis set is defined as the subset of participants in the FAS who have a baseline and Day 150 post-randomization QoL assessment. Participants in QoL analysis set with data available at given timepoint were analyzed.

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.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=165 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=130 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Change From Baseline in Global Health Status Scores Score at Baseline	68.6 Score on scale Standard Deviation 19.9	70.1 Score on scale Standard Deviation 23.1
Change From Baseline in Global Health Status Scores Change from Baseline at Study Day 50	-7.4 Score on scale Standard Deviation 20.2	-8.5 Score on scale Standard Deviation 22.7
Change From Baseline in Global Health Status Scores Change from Baseline at Study Day 100	1.3 Score on scale Standard Deviation 19.6	-15.3 Score on scale Standard Deviation 22.7
Change From Baseline in Global Health Status Scores Change from Baseline at Study Day 150	5.9 Score on scale Standard Deviation 24.9	-4.2 Score on scale Standard Deviation 23.7
Change From Baseline in Global Health Status Scores Change from Baseline at Study Month 9	8.0 Score on scale Standard Deviation 22.7	3.5 Score on scale Standard Deviation 23.7
Change From Baseline in Global Health Status Scores Change from Baseline at Study Month 12	8.6 Score on scale Standard Deviation 24.9	9.1 Score on scale Standard Deviation 20.2
Change From Baseline in Global Health Status Scores Change from Baseline at Study Month 15	9.0 Score on scale Standard Deviation 22.3	9.9 Score on scale Standard Deviation 18.9
Change From Baseline in Global Health Status Scores Change from Baseline at Study Month 18	10.2 Score on scale Standard Deviation 20.9	6.5 Score on scale Standard Deviation 21.3
Change From Baseline in Global Health Status Scores Change from Baseline at Study Month 21	10.0 Score on scale Standard Deviation 21.5	15.0 Score on scale Standard Deviation 19.6
Change From Baseline in Global Health Status Scores Change from Baseline at Study Month 24	8.6 Score on scale Standard Deviation 21.0	13.2 Score on scale Standard Deviation 17.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=164 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=131 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Change From Baseline in EORTC QLQ-C30 Physical Functioning Score Score at Baseline	83.5 Score on scale Standard Deviation 17.7	85.3 Score on scale Standard Deviation 18.9
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	-8.3 Score on scale Standard Deviation 17.5
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	-15.0 Score on scale Standard Deviation 19.1
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	-5.2 Score on scale Standard Deviation 21.3
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	-2.4 Score on scale Standard Deviation 23.5
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	0.4 Score on scale Standard Deviation 20.3
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	1.6 Score on scale Standard Deviation 16.1
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	3.2 Score on scale Standard Deviation 17.9
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	4.3 Score on scale Standard Deviation 21.4
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	5.6 Score on scale Standard Deviation 8.0

SECONDARY outcome

Timeframe: 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.

The Euro-QOL, Five Dimensions, Five Levels (EQ-5D-5L) questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). The total score for EQ-5D-5L index- is presented on a range from 0 to 1 where higher scores indicate better outcome. A positive change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=165 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=131 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Score at Baseline	0.803 Score on scale Standard Deviation 0.210	0.799 Score on scale Standard Deviation 0.250
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Day 50	-0.049 Score on scale Standard Deviation 0.205	-0.003 Score on scale Standard Deviation 0.198
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Day 100	0.012 Score on scale Standard Deviation 0.191	-0.068 Score on scale Standard Deviation 0.246
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Day 150	0.050 Score on scale Standard Deviation 0.212	0.014 Score on scale Standard Deviation 0.208
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Month 9	0.064 Score on scale Standard Deviation 0.190	0.015 Score on scale Standard Deviation 0.197
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Month 12	0.072 Score on scale Standard Deviation 0.241	0.051 Score on scale Standard Deviation 0.200
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Month 15	0.051 Score on scale Standard Deviation 0.209	0.080 Score on scale Standard Deviation 0.125
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Month 18	0.094 Score on scale Standard Deviation 0.180	0.072 Score on scale Standard Deviation 0.188
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Month 21	0.089 Score on scale Standard Deviation 0.235	0.110 Score on scale Standard Deviation 0.177
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score Change from Baseline at Study Month 24	0.051 Score on scale Standard Deviation 0.239	0.117 Score on scale Standard Deviation 0.138

SECONDARY outcome

Timeframe: Baseline, Days 50, 100, 150; Months 9, 12, 18, 21 and 24

Population: Participants in QoL analysis set with data available at given timepoint were analyzed.

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.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=165 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy n=129 Participants Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Change From Baseline in EQ-5D-5L VAS Scale Score Score at Baseline	72.4 Score on scale Standard Deviation 18.7	74.4 Score on scale Standard Deviation 20.1
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	-4.4 Score on scale Standard Deviation 16.7
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	-8.2 Score on scale Standard Deviation 19.8
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	-2.2 Score on scale Standard Deviation 22.2
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	4.4 Score on scale Standard Deviation 19.0
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	6.6 Score on scale Standard Deviation 17.8
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	8.2 Score on scale Standard Deviation 13.7
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	9.3 Score on scale Standard Deviation 13.6
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	10.1 Score on scale Standard Deviation 14.3
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	12.2 Score on scale Standard Deviation 15.3

SECONDARY outcome

Timeframe: From first dose of axicabtagene up to a median follow-up: 24 months

Population: Participants in SAS were analyzed.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=170 Participants Participants received conditioning chemotherapy regimen consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day (day -5 to day -3) for 3 days followed by 2 rest days (day -2 \& day -1) and then received a single infusion of axicabtagene ciloleucel administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg on treatment Day 0.	Standard of Care Therapy Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Number of Participants With Anti-Axicabtagene Ciloleucel Antibodies	0 Participants	—

SECONDARY outcome

Timeframe: Up to 5 years

A TEAE is defined as any AE that begins on or after the first dose of study treatment (axicabtagene ciloleucel infusion or SOC), excluding bridging therapy. Participant incidence rates of TEAEs, including all, serious, fatal, CTCAE Grade 3 or higher, and treatment related AEs reported will be tabulated by preferred term and system organ class coded with the Medical Dictionary for Regulatory Activities (MedDRA).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

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.

Outcome measures

Outcome data not reported

Adverse Events

Axicabtagene Ciloleucel

Serious events: 95 serious events

Other events: 170 other events

Deaths: 82 deaths

Standard of Care Therapy

Serious events: 78 serious events

Other events: 166 other events

Deaths: 95 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information

Kite, A Gilead Company

Phone: 844-454-5483 (1-844-454-KITE)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Axicabtagene Ciloleucel n=170 participants at risk Participants received cyclophosphamide 500 mg/m\^2/day IV and fludarabine 30 mg/m\^2/day IV 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-cluster of differentiation antigen (CD) 19 CAR transduced autologous T cells/kg on Day 0.	Standard of Care Therapy n=168 participants at risk Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Blood and lymphatic system disorders Anaemia	1.2% 2/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	1.8% 3/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Coagulopathy	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Febrile neutropenia	3.5% 6/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	13.1% 22/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Leukopenia	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Neutropenia	2.4% 4/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Acute myocardial infarction	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Atrial fibrillation	2.9% 5/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	1.2% 2/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Cardiac arrest	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Cardiac failure	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Cardiomyopathy	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Myocardial infarction	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Pericardial effusion	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Sinus tachycardia	1.2% 2/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	1.2% 2/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Tachycardia	1.2% 2/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Ventricular tachycardia	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Eye disorders Vision blurred	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Abdominal pain	1.8% 3/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	1.2% 2/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Colitis	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Dysphagia	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Enterocolitis	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Enterovesical fistula	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Food poisoning	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Ileus	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Nausea	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	1.2% 2/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Oesophageal fistula	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Oral disorder	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Stomatitis	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Vomiting	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Chest pain	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Chills	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Fatigue	1.8% 3/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Incarcerated hernia	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Influenza like illness	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.

Other adverse events
Measure	Axicabtagene Ciloleucel n=170 participants at risk Participants received cyclophosphamide 500 mg/m\^2/day IV and fludarabine 30 mg/m\^2/day IV 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-cluster of differentiation antigen (CD) 19 CAR transduced autologous T cells/kg on Day 0.	Standard of Care Therapy n=168 participants at risk Participants received 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m\^2 before chemotherapy,ifosfamide 5 g/m\^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m\^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m\^2 Day 1,etoposide 40 mg/m\^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m\^2/day Days 1-4,cytarabine 2 g/m\^2 on Day 5; R-GDP: rituximab 375 mg/m\^2 Day 1(or Day 8),gemcitabine 1g/m\^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m\^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m\^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m\^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m\^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m\^2. Participants who responded got high dose therapy and autologous stem cell transplant up to 60 months.
Blood and lymphatic system disorders Anaemia	41.8% 71/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	53.6% 90/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	14.3% 24/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Leukopenia	5.3% 9/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	3.6% 6/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Neutropenia	44.1% 75/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	16.7% 28/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Blood and lymphatic system disorders Thrombocytopenia	12.9% 22/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	23.8% 40/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Sinus tachycardia	34.1% 58/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	9.5% 16/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Cardiac disorders Tachycardia	7.6% 13/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	6.0% 10/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Ear and labyrinth disorders Tinnitus	0.00% 0/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	6.5% 11/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Abdominal distension	2.4% 4/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	6.5% 11/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Abdominal pain	13.5% 23/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	13.7% 23/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Constipation	20.0% 34/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	34.5% 58/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Diarrhoea	41.8% 71/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	39.3% 66/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Dry mouth	9.4% 16/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	4.8% 8/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Dyspepsia	2.9% 5/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	8.3% 14/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Nausea	40.0% 68/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	69.0% 116/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Stomatitis	2.4% 4/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	17.3% 29/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Gastrointestinal disorders Vomiting	19.4% 33/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	32.7% 55/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Asthenia	8.2% 14/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	9.5% 16/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Chills	27.1% 46/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	8.3% 14/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Fatigue	40.6% 69/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	51.8% 87/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Malaise	8.8% 15/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	5.4% 9/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Mucosal inflammation	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	8.9% 15/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Oedema peripheral	11.8% 20/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	16.7% 28/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
General disorders Pyrexia	87.6% 149/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	23.8% 40/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Hepatobiliary disorders Hypertransaminasaemia	6.5% 11/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Immune system disorders Hypogammaglobulinaemia	11.2% 19/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.60% 1/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Infections and infestations Oral candidiasis	8.2% 14/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	3.0% 5/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Infections and infestations Upper respiratory tract infection	5.3% 9/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	3.0% 5/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Injury, poisoning and procedural complications Infusion related reaction	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	7.1% 12/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Alanine aminotransferase increased	18.2% 31/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	9.5% 16/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Aspartate aminotransferase increased	14.1% 24/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	8.9% 15/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Blood alkaline phosphatase increased	5.9% 10/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	8.3% 14/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Blood creatinine increased	5.9% 10/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	8.9% 15/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations C-reactive protein increased	8.8% 15/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	2.4% 4/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Lymphocyte count decreased	18.2% 31/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	12.5% 21/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Neutrophil count decreased	30.0% 51/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	26.8% 45/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Platelet count decreased	17.6% 30/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	38.1% 64/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Serum ferritin increased	8.8% 15/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	0.00% 0/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Weight decreased	6.5% 11/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	3.6% 6/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.
Investigations Weight increased	0.59% 1/170 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.	7.1% 12/168 • Up to 59.3 months All-Cause Mortality: The Full Analysis Set consisted of all randomized participants. Adverse Events: The Safety Analysis Set is 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.