3‐Year outcomes of adults with relapsed or refractory B‐cell acute lymphoblastic leukemia treated with brexu‐cel in ZUMA‐3 by age, prior therapies, and subsequent transplant (2023)

Background: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the US for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and in the EU for adults ≥26 years with R/R B-ALL based on positive results of ZUMA-3. After 3-years follow-up in ZUMA-3, brexu-cel demonstrated an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 71% and a median overall survival (OS) of 26.0 mo in all treated pts (N = 55) and 38.9 mo in pts with CR (n = 31; Shah et al. EU CAR T 2023. Abstract 34). Here we report 3-years outcomes by age, prior therapies, and subsequent allogeneic stem cell transplant (alloSCT). Methods: Pts (≥18 years) had R/R B-ALL and received 1 brexu-cel infusion (1×10⁶ CAR T cells/kg) following leukapheresis and conditioning chemotherapy. The primary endpoint was overall CR/CRi rate per independent review. Post hoc subgroup analyses were exploratory, with descriptive statistics reported. Results: As of July 23, 2022, the median follow-up in Phase 2 (N = 55) was 38.8 mo (range, 32.7–44.6). The CR/CRi rate (95% CI) was 67% (35–90) for pts <26 years (n = 12) and 72% (56–85) for pts ≥26 years (n = 43). The median (95% CI) OS was 28.6 mo (0.6-not estimable [NE]) for pts <26 years and 34.1 mo (15.9-NE) for pts ≥26 years. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 92% of pts <26 years and in 88% of pts ≥26 years. For pts with 1 prior therapy (n = 10), the CR/CRi rate was 90% (95% CI, 55–100) and for pts with ≥2 prior therapies (n = 45), the CR/CRi rate was 67% (95% CI, 51–80); medians (95% CI) for OS were not reached (NR; 2.1-NE) and 25.6 mo (14.2–38.9), respectively. The incidence of Grade ≥3 TRAEs was 90% for pts with 1 prior therapy and 89% for pts with ≥2 prior therapies. The CR/CRi rates (95% CI) for pts with (n = 25) and without (n = 30) prior blinatumomab (blina) were 60% (39–79) and 80% (61–92). The median (95% CI) OS was 14.2 mo (3.2–26.0) for pts with prior blina and NR (18.6-NE) for pts without prior blina; Grade ≥3 TRAEs occurred in 80% and 97% of pts, respectively. For responders (CR/CRi) who did (n = 10) or did not (n = 29) proceed to subsequent alloSCT, the median (95% CI) OS was NR (7.6-NE) and 38.9 mo (18.6-NE), respectively. Similar efficacy results were observed in a pooled subgroup analysis of Phase 1 and 2 pts treated at the pivotal dose (N = 78), with a median follow-up of 41.6 mo (range, 32.7–70.3). Conclusions: Adults with R/R B-ALL benefitted from brexu-cel, regardless of age, number of prior therapies, prior blina exposure, or subsequent alloSCT status. Survival appeared longer in pts with fewer prior therapies and in blina-naïve pts; however, small pt numbers and unmatched baseline characteristics limit interpretation of these results. Additional studies are needed to determine the impact of prior therapies and/or subsequent alloSCT on outcomes of pts who receive brexu-cel. Encore Abstract - previously submitted to ASCO 2023 and EHA 2023 The research was funded by: The research was funded by: Kite, a Gilead Company Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Immunotherapy Conflicts of interests pertinent to the abstract. B. D. Shah Consultant or advisory role: Adaptive, Amgen, Autolus, Beigene, BMS, Century Therapeutics, Deciphera, Jazz, Kite, a Gilead Company, Lilly, Novartis, Precision Biosciences, Pfizer, and Takeda Research funding: Jazz Pharmaceuticals, Kite and Servier Other remuneration: PeproMene Bio R. D. Cassaday Employment or leadership position: (Immediate family member): Seagen Consultant or advisory role: Amgen and Kite, a Gilead Company Stock ownership: (Immediate family member): Seagen Honoraria: Amgen, Jazz, Kite, and Pfizer Research funding: Amgen, Kite, Merck, Pfizer, Servier, and Vanda Educational grants: Kite Other remuneration: Autolus (independent review committee) and Pepromene Bio (DSMB) J. H. Park Consultant or advisory role: AstraZeneca, Kite, a Gilead Company, and Novartis Research funding: Amgen, Genentech, and Juno R. Houot Consultant or advisory role: Kite, a Gilead Company and Gilead Honoraria: ADC therapeutics, Bristol-Myers Squibb, Celgene, Gilead Sciences, Janssen, Kite, MSD, and Novartis N. Boissel Consultant or advisory role: Amgen, Kite, a Gilead Company, and Novartis Honoraria: Amgen, Kite, and Novartis Research funding: Amgen Other remuneration: Expert testimony for Amgen T. Leguay Consultant or advisory role: Amgen, Incyte, and Servier Honoraria: Amgen, Incyte, Kite, a Gilead Company, and Servier M. R. Bishop Consultant or advisory role: Novartis, Kite/Gilead, Bristol-Myers Squibb, Sana Bio, CRISPR Therapeutics Honoraria: Incyte, Bristol-Myers Squibb, Sanofi, ADC Therapeutics Other remuneration: Speakers' bureau participation for Incyte, Bristol-Myers Squibb, Sanofi, and ADC Therapeutics M. S. Topp Consultant or advisory role: AstraZeneca, Bristol Myers Squibb, GenMaB, Kite, a Gilead Company, and Roche Research funding: Kite, Regeneron, Roche, and Takeda Educational grants: Janssen and Kite M. R. Baer Research funding: Abbvie, Ascentage, Kite, a Gilead company, Kura, and Takeda G. J. Schiller Honoraria: Kite, a Gilead Company Research funding: Kite Other remuneration: Speakers' bureau participation for Kite M. Abedi Consultant or advisory role: Celgene Honoraria: Celgene Other remuneration: Speakers’ bureau participation for Abbvie, Bristol Myers Squibb, Celgene, and Kite, a Gilead Company M. C. Minnema Consultant or advisory role: (To your institution): Bristol Myers Squibb, CDR-life, GSK, and Janssen-Cilag Research funding: (To your institution): Beigene Other remuneration: Speaker's bureau participation for WebMD P. Stiff Consultant or advisory role: MorphoSys and CRISPR Therapeutics Honoraria: MorphoSys and CRISPR Therapeutics Research funding: Amgen, Gamida Cell, Pfizer, Karyopharm, Gilead Sciences, Incyte, Seagen, and Cellectar L. Zhou Employment or leadership position: Kite, a Gilead Company Stock ownership: AbbVie RSU T. Hadjivassileva Employment or leadership position: Kite, a Gilead Company Stock ownership: Kite R. Damico Khalid Employment or leadership position: Kite, a Gilead Company Stock ownership: Kite Educational grants: Kite A. Armin Ghobadi Consultant or advisory role: Amgen, Atara, BMS, CRISPR therapeutics, Kite, a Gilead Company, and Wugen Inc. Honoraria: Kite Research funding: Amgen, Genentech, and Kite