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

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

Time frame: Up to 4 years

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

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

Time frame: 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.

Time frame: 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.

Time frame: Up to Week 4

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

Grading categories were determined by CTCAE version 5.0.

Time frame: 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.

Time frame: Up to 2 years

Population: Participants in the Safety Analysis Set were analyzed.

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.

Time frame: Up to 2 years

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

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

Time frame: Up to Month 24

Population: Participants in the Safety Analysis Set were analyzed.

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.

Time frame: 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.

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.

Time frame: Up to 4 years

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

Time frame: Up to Week 4

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