Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies

All Substudies (Substudies A, B, C and D): Complete Response (CR) Rate Determined by Central Assessment

CR Rate is defined as the percentage of participants with CR.

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Duration of Response (DOR)

DOR was defined as time from first objective response (OR) to disease progression (PD) or death. OR is defined in OM#25 (Substudy B), 28 (Substudy C), and 29 (Substudy D). PD: 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.

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Overall Survival (OS)

OS was defined as the time from the date of brexucabtagene autoleucel infusion to the date of death from any cause.

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Progression Free Survival (PFS)

PFS was defined as the time from the date of brexucabtagene autoleucel infusion to the date of PD or death from any cause. PD is defined in outcome measure #6.

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Time to Next Treatment (TTNT)

TTNT defined as the time from the date of brexucabtagene autoleucel infusion to the start of new anti-cancer (including stem cell transplant) therapy prior to documented progression, or death from any cause. KM estimates were used in the outcome measure analysis.

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Time to First Objective Response

Time to first objective response was defined as time from the date of brexucabtagene autoleucel infusion to the date of first response per the Sixth International Workshop in WM for r/rWM, per the Lugano Classification for r/rRT and r/r BL, and per Grever and colleagues for r/rHCL. Objective response (OR) is defined in OM#25 (Substudy B), 28 (Substudy C), and 29 (Substudy D).

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Time to Best Objective Response

Time to best objective response was defined as time from the date of brexucabtagene autoleucel infusion to the date of best response per the Sixth International Workshop in WM for r/rWM, per the Lugano Classification for r/rRT and r/r BL, and per Grever and colleagues for r/rHCL. Objective response (OR) is defined in OM#25 (Substudy B), 28 (Substudy C), and 29 (Substudy D).

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

TEAE was defined as any adverse event with onset on or after the brexucabtagene autoleucel infusion.

Time frame: First infusion date of brexucabtagene autoleucel up to 2 years

All Substudies (Substudies A, B, C and D): Number of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher

Laboratory results were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CTCAE grading is a standardized system from the NCI that classifies the severity of side effects (adverse events) from cancer treatments, using a 1-5 scale: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death) The incidence of post-infusion worst-grade lab toxicities for all analytes were summarized.

Time frame: First infusion date of brexucabtagene autoleucel up to 2 years

All Substudies (Substudies A, B, C and D): Number of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher

Laboratory results were graded according to NCI CTCAE version 5.0. The incidence of post-infusion worst-grade lab toxicities for all analytes were summarized.

Time frame: First dose date up to 2 years

All Substudies (Substudies A, B, C and D): Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs)

Dose-limiting toxicity is defined as protocol-defined brexucabtagene autoleucel-related events with onset within the first 28 days following brexucabtagene autoleucel infusion.

Time frame: First infusion date of brexucabtagene autoleucel up to 28 days

All Substudies (Substudies A, B, C and D): Number of Participants With Positive Anti-brexucabtagene Autoleucel Antibodies

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Number of Participants With Replication-competent Retrovirus (RCR) in Peripheral Blood Mononuclear Cells (PBMCs)

Time frame: Up to 2 years

All Substudies (Substudies A, B, C and D): Number of Participants With Deterioration Scores From Screening in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30)

EORTC QLQ-C30 is a quality of life (QOL) questionnaire for cancer participants, that has 30 items. 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, and financial difficulties). Scoring of the QLQ-C30 was performed according to QLQ-C30 Scoring manual. Participants with deterioration scores from screening for various questions of EORTC QLQ C-30 are reported. Deterioration was defined as scores at specific time point lesser than scores at baseline.

Time frame: Day -5, Day 0, Day 28, Month 3, Month 6, Month 9 and Month 12

All Substudies (Substudies A, B, C and D): Number of Participants With Deterioration Scores From Screening in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L)

EQ-5D-5L was an instrument for use as a measure of health outcome. The EQ-5D-5L consisted of 2 sections: EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). EQ-5D comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Number of participants with deterioration scores from screening for each category are reported. Deterioration was defined as scores at specific time point lesser than scores at baseline.

Time frame: Day -5, Day 0, Day 28, Month 3, Month 6, Month 9 and Month 12

All Substudies (Substudies A, B, C and D): Change From Screening in the EQ-ED-5L Visual Analogue Scale (EQ-VAS) Score

The EQ-VAS recorded the participant's self-rated health on a vertical VAS, where the end points were labeled "the best health you can imagine" and "the worst health you can imagine." The EQ-VAS could be used as a quantitative measure of a health outcome that reflected the participant's own judgment. The EQ-VAS recorded the participant's self-rated health on a vertical VAS, with a score numbered from 0 to 100, where '100 meant the best health you can imagine' and '0 meant the worst health you can imagine".

Time frame: Screening, Day -5, Day 0, Day 28, Month 3, Month 6, Month 9 and Month 12

Substudy A: ORR (CR, VGPR, or PR) Determined by Central Assessment Per the Sixth International Workshop in WM

ORR was defined as the percentage of participants who achieved a best response of CR, VGPR, or PR per the Sixth International Workshop in WM.

Time frame: Up to 2 years

Substudy A: Percentage of Participants With Combined CR and VGPR Determined by Investigator Assessment Per the Sixth International Workshop in WM

The combined rate of CR and VGPR was defined as the percentage of participants who achieved a best response of either CR or VGPR.

Time frame: Up to 2 years

Substudy A: PR Rate Determined by Central Assessment Per the Sixth International Workshop in WM

PR rate was defined as percentage of participants who achieve PR.

Time frame: Up to 2 years

Substudy A: VGPR Rate Determined by Central Assessment Per the Sixth International Workshop in WM

VGPR rate was defined as percentage of participants who achieve VGPR.

Time frame: Up to 2 years

Substudy B: Number of Participants With OR Determined by Investigator Assessment Per the Lugano Classification

OR: CR (complete metabolic response (CMR)+complete radiological response (CRR))+PR (partial MR response (PMR)+partial RR(PRR)). CMR: score 1(no uptake above background)/2(uptake≤mediastinum)/3(uptake \>mediastinum but ≤liver)with/without a residual mass on positron emission tomography 5-point scale;no new lesions,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;bone marrow normal by morphology. PMR:score 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. PRR:≥50% decrease in sum of product of diameters up to 6 target nodes and extra-nodal sites;absent/ normal,regressed,but no increase of NMLs;spleen regressed by\>50% in length beyond normal.

Time frame: Up to 2 years

Substudy B: Number of Participants With OR Based on Clonal Relationship to the Underlying CLL by Central Assessment Per the Lugano Classification

OR is defined as participants with CR or PR.

Time frame: Up to 2 years

Substudy B: Number of Participants With OR (CR, CRi, or PR) Determined by Investigator Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 Criteria

OR was defined as the number of participants who achieved a best response of either CR, CRi, or PR by investigator assessment per IWCLL 2018 criteria. CR: Lymph nodes- none ≥1.5 cm; Liver or spleen size- Spleen size \<13 cm; liver size normal; Constitutional symptoms, Circulating lymphocyte count- none; Platelet count- ≥100 × 109/L; Hemoglobin- ≥11.0 g/dL (untransfused and without erythropoietin); Marrow- Normocellular, no CLL cells, no B-lymphoid nodules. CRi: ; PR: Lymph nodes- Decrease ≥50% (from baseline); Liver or spleen size- Decrease ≥50% (from baseline); Constitutional symptoms- any, Circulating lymphocyte count- Decrease ≥50% from baseline; Platelet count- ≥100 × 109/L or increase ≥50% over baseline; Hemoglobin-≥11 g/dL or increase ≥50% over baseline; Marrow- Presence of CLL cells, or of B-lymphoid nodules, or not done.

Time frame: Up to 2 years

Substudy C: Number of Participants With OR Determined by Investigator Assessment Per the Lugano Classification

OR was defined as the number of participants who achieved a best response of either CR or PR per the Lugano Classification. CR and PR per Lugano classification is defined in outcome measure #25.

Time frame: Up to 2 years

Substudy D: Number of Participants With OR Determined by Investigator Assessment Per Grever and Colleagues

OR was defined as the number of participants who achieved a best response of either CR or PR per Grever and colleagues. CR: Near normalization of peripheral blood counts: hemoglobin \>11 g/dL (without transfusion); platelets\>100 000/μL; absolute neutrophil count \>1500/μL. Regression of splenomegaly on physical examination. Absence of morphologic evidence of HCL on both the peripheral blood smear and the bone marrow examination. PR: PR required near normalization of the peripheral blood count (as in CR) with a minimum of 50% improvement in organomegaly and bone marrow biopsy infiltration with HCL.

Time frame: Up to 2 years