Trial Outcomes & Findings for Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3) (NCT NCT04880434)

Participants were enrolled at study sites in France, Germany, Netherlands, Spain, the United Kingdom, and the United States.

Out of 254 participants screened for the overall KTE-C19-102 study, 95 participants were enrolled for Cohort 3 of this study. Results for KTE-C19-102, Cohorts 1 and 2 were reported in NCT02601313, and results for Cohort 3 (NCT04880434) are reported in this study.

Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)

OR: complete metabolic response (CMR),complete radiological response (CRR), 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 ≤1.5cm 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 (EOT). PRR: ≥50% decrease in sum of the product of the 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.

DOR: time from the first OR to progressive disease (PD)/death. It was determined using Kaplan-Meier (KM) estimates. 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; new FDG-avid foci consistent with lymphoma rather than another etiology; new/recurrent FDG-avid foci 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 (PPD) nadir, increase in LDi or shortest axis perpendicular to the LDi from nadir, the splenic length must increase by \> 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, the increase must be ≥ 2 cm from baseline; new/recurrent splenomegaly; new or clear progression of pre-existing NMLs; new lesion; new/recurrent bone marrow involvement.

BOR consisted of complete response (CR), partial response (PR), stable disease (SD), PD, not done and not evaluable (NE). CR=CMR/CRR and PR=PMR/PRR were defined in Outcome Measure (OM) 1. SD/no metabolic response (NMR): a score 4 (uptake moderately greater than (\>) liver) or 5 (uptake markedly \>liver and/ or new lesions) with no significant change in FDG uptake compared to baseline (screening), at an interim time point or end of treatment; no new sites of disease should be observed. PD was defined in OM 2. Not done: no assessment at the time of analysis. Clopper-Pearson method was used for OM analysis. Percentages were rounded off.

OR was defined in OM #1. Percentages were rounded-off.

PFS was defined as the time from brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD was defined in OM #2. Kaplan-Meier (KM) estimates were used for analysis.

OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. KM estimates were used for analysis.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participants. The event did not necessarily have a relationship with study treatment. AE included worsening of a pre-existing medical condition. Worsening indicated that the pre-existing medical condition had increased in severity, frequency, and/or duration or had an association with a worse outcome. A pre-existing condition that had not worsened during the study or involved an intervention such as elective cosmetic surgery or a medical procedure while on study, was not considered an AE. TEAE was defined as any AE with onset on or after the start of treatment.

Laboratory results were graded according to National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE) version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.

Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.

Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.

Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.

Peak was defined as the maximum post-baseline level of the cytokine.

Peak was defined as the maximum post-baseline level of the cytokine.

Peak was defined as the maximum post-baseline level of the cytokine.

The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) was a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant was asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, were converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. Percentage of participants with each scale score for all 5 dimensions are reported. Percentages were rounded-off.

EQ-5D was a standardized participant completed questionnaire that measures health-related quality of life and translated the score into an index value or utility score. EQ-5D-consisted of two components: a health state profile and an optional visual analogue scale (VAS). The EQ-5D-VAS recorded the participant's self-rated health on a vertical visual analogue scale, where the endpoints were labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicated better self-reported health status.

EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status/quality of life (QoL) scale, symptom scales (fatigue, pain, nausea/vomiting), and single items scales (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged, transformed to 0-100 scale. Higher scores for functional scales and for the global health status/QoL scale indicate a higher level of functioning and a better health-related QoL, whereas higher scores in symptom scales represent a higher level of symptoms. Deterioration of score was defined as worsened by at least 1 level from screening. Participants with answer "Yes" to the EORTC functional scale questionnaire were reported.