Trial Outcomes & Findings for Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies (NCT NCT05537766)

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

29 participants were screened (Substudy A:1; Substudy B: 10; Substudy C: 16; Substudy D: 2). Substudy A was withdrawn, prior to enrollment of any participants. Therefore, the results below are reported only for Substudies B, C, and D.

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

The combined rate of CR and VGPR was defined as the percentage of participants who achieved a best response of either CR or VGPR per the Sixth International Workshop in WM.

ORR was defined as the percentage of participants who achieved a best response of either CR or PR per the Lugano Classification.

ORR was defined as the percentage of participants who achieved a best response of either CR or PR per the Lugano Classification.

ORR was defined as the percentage 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.

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

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.

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

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.

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 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 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).

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

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.

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.

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

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.

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.

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".

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.

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

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

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

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.

OR is defined as participants with CR or PR.

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.

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.

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.