Session: 905. Outcomes Research—Lymphoid Malignancies: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Lymphomas, non-Hodgkin lymphoma, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies
Methods: Individual patient-level data were available for ZUMA-2 (N=68; 35.8 months median follow-up as of July 24, 2021 data cut-off) whereas study-level data were available for BRUIN (N=90 in the BTKi pre-treated cohort; 23.5 months median follow-up as of July 29, 2022 data cut-off). Longer-term overall survival (OS) data for ZUMA-2 from the July 23, 2022 data cut-off (46.1 months median follow-up) were available and used. Logistic propensity score models were used to weight the brexu-cel infused population from ZUMA-2 to match the aggregate baseline characteristics of the BTKi pre-treated cohort in BRUIN. These baseline characteristics represented clinically relevant prognostic factors which were pre-specified based on input from clinical experts and data availability. The base-case model incorporated the top five most pertinent factors, which were reported in at least 50% of patients in both trials: blastoid morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplantation. A sensitivity analysis additionally incorporated TP53 mutation (missing in >50% of patients in ZUMA-2 and BRUIN) and Ki-67 proliferation index (missing in >50% of patients in BRUIN). Several prognostic factors (response to prior BTKi therapy, response to last therapy, and duration on prior BTKi therapy) could not be considered due to not being reported for BRUIN. The effective sample size was calculated as a measure of the degree of precision after weighting, reflecting the extent of overlap in the distribution of covariates between the trial populations. Relative treatment effects were expressed as odds ratios or hazard ratios with 95% confidence intervals. Outcomes included objective response (ORR), complete response (CR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Results: In the base-case MAIC, a significant difference in the odds of ORR and CR in favor of brexu-cel versus pirtobrutinib was observed (Table 1). Similarly, brexu-cel demonstrated a significant improvement in PFS (Table 2). OS and DOR point estimates were in favor of brexu-cel when compared to pirtobrutinib, although not statistically significant. These findings were consistent with unadjusted naïve analyses as well as the sensitivity analyses including adjustment for TP53 mutation and Ki-67 proliferation index.
Conclusions: While acknowledging the inherent limitations of an unanchored indirect comparison, our findings suggest that brexu-cel offers clinically and statistically significant efficacy benefits in terms of ORR, CR, and PFS compared to pirtobrutinib in patients with R/R MCL after prior cBTKi therapy. Both treatments were not statistically different in terms of OS and DOR although the estimated hazard ratios indicated a favorable trend for brexu-cel; however, given the relatively shorter follow-up and the high degree of censoring in BRUIN, an updated analysis incorporating longer follow-up data with more events from BRUIN could provide more reliable results. Although efforts were made to ensure a robust approach to the selection of prognostic factors for inclusion in the model, the possibility of some residual confounding variables cannot be completely ruled out. Nevertheless, these results provide valuable insights that may help inform treatment decisions for this population.
Disclosures: Chen: PRECISIONheor: Current Employment, Other: PRECISIONheor is a consultancy firm which received funding for this study from Kite, a Gilead Company. Zhang: PRECISIONheor: Current Employment, Other: PRECISIONheor is a consultancy firm which received funding for this study from Kite, a Gilead Company. Wu: Gilead Sciences: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Other; Abbott: Current holder of stock options in a privately-held company, Other; AbbVie: Current holder of stock options in a privately-held company, Other; Amgen: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Other; Avid: Current holder of stock options in a privately-held company, Other; Curis: Current holder of stock options in a privately-held company, Other; Viracta: Current holder of stock options in a privately-held company, Other. Wade: Kite, a Gilead Company: Consultancy; Abbvie: Consultancy. Nunes: Amgen: Current holder of stock options in a privately-held company; Gilead Sciences Europe Ltd: Current Employment, Current holder of stock options in a privately-held company, Honoraria. Peng: Gilead Sciences: Current Employment, Current equity holder in publicly-traded company. Snider: Kite/Gilead Sciences: Current Employment, Current equity holder in publicly-traded company. Maciel: PRECISIONheor: Current Employment, Other: PRECISIONheor is a consultancy firm which received funding for this study from Kite, a Gilead Company. Chan: PRECISIONheor: Current Employment, Other: PRECISIONheor is a consultancy firm which received funding for this study from Kite, a Gilead Company. Keeping: PRECISIONheor: Current Employment, Other: PRECISIONheor is a consultancy firm which received funding for this study from Kite, a Gilead Company. Shah: Moffitt Cancer Center: Current Employment; DSMC, Pepromene Bio: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/Janssen, Spectrum/Acrotech, BeiGene, Gilead Sciences: Honoraria; Incyte, Jazz Pharmaceuticals, Kite/Gilead, SERVIER: Research Funding; Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, AstraZeneca, Stemline Therapeutics, Kite/Gilead: Other: Travel, Accommodations, Expenses; Takeda, AstraZeneca, Adaptive Biotechnologies, BMS/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, Kite/Gilead, Jazz Pharmaceuticals, Century Therapeutics, Deciphera, Autolus Therapeutics, Lilly, Pepromene: Consultancy.
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