Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma (NCT NCT03761056)

Last Updated: 2024-12-04

Results Overview

CR Rate is the percentage of participants with CR (complete metabolic response (CMR); complete radiological response (CRR)). CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Up to 4 years

Results posted on

2024-12-04

Participant Flow

Participants were enrolled at study sites in the United States, France, and Australia.

54 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-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Overall Study STARTED	42
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	13

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-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Overall Study Death	8
Overall Study Enrolled but never treated	2
Overall Study Withdrawal of consent from further follow-up	2
Overall Study Investigator decision	1

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants
Age, Continuous	60.2 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	33 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	4 Participants n=5 Participants
Region of Enrollment United States	32 Participants n=5 Participants
Region of Enrollment France	2 Participants n=5 Participants
Region of Enrollment Australia	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Population: The Response Evaluable Analysis set included participants who were enrolled and treated with axicabtagene ciloleucel at a dose of at least 1 x 10\^6 anti-CD19 CAR T cells/kg, and centrally confirmed disease type (double-/triple- hit lymphomas) or International Prognostic Index (IPI) score ≥ 3.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=37 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators	86 percentage of participants Interval 71.0 to 95.0

SECONDARY outcome

Timeframe: Up to 4 years

Population: Participants in the Response Evaluable Analysis Set 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 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=37 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators	92 percentage of participants Interval 78.0 to 98.0

SECONDARY outcome

Timeframe: Up to 4 years

Population: Participants in the Response Evaluable Analysis Set who achieved ORR were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cutoff date or new anti-lymphoma therapy start (including stem cell transplant or retreatment of axicabtagene ciloleucel), whichever is 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 to disease progression (PD) (Lugano classification) or death from any cause. Objective response is defined in outcome measure (OM) 2. PD is defined as a score 4 (uptake moderately \> liver) or 5 (uptake markedly \>liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. Kaplan-Meier (KM) estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=34 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Duration of Response (DOR) Per the Lugano Classification	NA months Median, upper and lower limits of confidence interval (CI) were not estimable as participants were censored.

SECONDARY outcome

Timeframe: Up to 4 years

EFS was defined as the time from axicabtagene ciloleucel infusion date to earliest date of disease progression (Lugano classification), commencement of subsequent new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD is defined in OM 3. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=37 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Event-Free Survival (EFS)	NA months Median, upper and lower limits of CI were not estimable as participants were censored.

SECONDARY outcome

Timeframe: Up to 4 years

Population: Participants in the Response Evaluable Analysis Set were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cutoff date or new antilymphoma therapy start date (including stem cell transplant or retreatment of axicabtagene ciloleucel) whichever was earlier.

PFS was defined as the time from axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause. PD is defined in OM 3. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=37 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Progression-Free Survival (PFS)	NA months Median, upper and lower limits of CI were not estimable as participants were censored.

SECONDARY outcome

Timeframe: Up to 4 years

Population: Participants in the Response Evaluable Analysis Set were analyzed.

OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=37 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Overall Survival (OS)	NA months Median, upper and lower limits of CI were not estimable due to low number of events.

SECONDARY outcome

Timeframe: Up to 2 years

Population: Safety Analysis Set included all participants treated with any dose of study drug.

An AE was any untoward medical occurrence in a participant in a clinical trial participant, which did not necessarily have a causal relationship with the treatment. Treatment-emergent adverse events were defined as any adverse event with onset on or after the axicabtagene ciloleucel infusion. Serious adverse event was defined as an event that resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; and medically important event or reaction.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE) TEAEs	100 percentage of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE) Treatment-Emergent SAE	55 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Participants in the Safety Analysis Set were analyzed.

Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Hemoglobin	3 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Alanine Aminotransferase	8 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Alkaline Aminotransferase	0 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Aspartate Aminotransferase	5 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Bilirubin	20 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Calcium	5 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Creatinine	5 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Glucose	15 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Magnesium	5 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Sodium	0 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value Urate	18 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Participants in the Safety Analysis Set were analyzed.

Grading categories were determined by CTCAE version 5.0.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Hemoglobin	43 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Leukocytes	93 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Lymphocytes	75 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Neutrophils	95 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Platelets	25 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Albumin	3 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Calcium	10 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Glucose	0 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Magnesium	3 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Potassium	5 percentage of participants
Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value Sodium	23 percentage of participants

SECONDARY outcome

Timeframe: Up to 4 years

Population: Participants in the Response Evaluable Analysis Set with available data were analyzed.

Relapse with CNS disease was defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of CNS involvement with lymphoma as determined by typical symptoms, cerebrospinal fluid (CSF) evaluation, and/or diagnostic imaging.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=37 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Relapse With Central Nervous System (CNS) Disease	0 months Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Up to Month 24

Population: Participants in the Safety Analysis Set were analyzed.

Peak was defined as the maximum number of CAR T cells in blood measured after infusion.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood	36.27 cells/µL Interval 20.51 to 133.96

SECONDARY outcome

Timeframe: Up to Week 4

Population: Participants in the Safety Analysis Set with data available were analyzed.

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 Granzyme B	28.5 pg/mL Interval 11.8 to 75.6
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 IFNg	409.4 pg/mL Interval 157.8 to 856.8
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 IL-2	16.4 pg/mL Interval 9.7 to 32.9
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 IL-5	6.3 pg/mL Interval 6.3 to 26.2
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 IL-6	35.1 pg/mL Interval 13.2 to 181.1
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8 IL-8	63.0 pg/mL Interval 30.1 to 107.5

SECONDARY outcome

Timeframe: Up to Week 4

Population: Participants in the Safety Analysis Set with data available were analyzed.

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Peak Serum Level of C-Reactive Protein (CRP)	208.4 mg/L Interval 60.9 to 407.5

SECONDARY outcome

Timeframe: Up to Week 4

Population: Participants in the Safety Analysis Set with data available were analyzed.

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Peak Serum Level of Ferritin	749.1 ng/mL Interval 473.9 to 1874.3

SECONDARY outcome

Timeframe: Up to Week 4

Population: Participants in the Safety Analysis Set with data available were analyzed.

Time to peak is defined as the number of days from axicabtagene ciloleucel infusion to the date when the cytokine first reached the maximum post-baseline level.

Outcome measures

Outcome measures
Measure	Axicabtagene Ciloleucel n=40 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 T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin Granzyme B	8 days Interval 8.0 to 8.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin IFNg	4 days Interval 4.0 to 8.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin IL-2	4 days Interval 4.0 to 4.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin IL-5	1 days Interval 1.0 to 4.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin IL-6	8 days Interval 4.0 to 8.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin IL-8	8 days Interval 4.0 to 8.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin CRP	4 days Interval 4.0 to 8.0
Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin Ferritin	8 days Interval 6.0 to 8.0

Adverse Events

Axicabtagene Ciloleucel

Serious events: 22 serious events

Other events: 40 other events

Deaths: 7 deaths

Retreatment Axicabtagene Ciloleucel

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 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