Outcomes following brexucabtagene autoleucel administered as an FDA-approved therapy for adults with relapsed/refractory B-ALL.

person Gregory Roloff University of Chicago, Chicago, IL info_outline Gregory Roloff, Rawan Faramand, Ibrahim Aldoss, Noam Edward Kopmar, Marc Schwartz, Simone E. Dekker, Chenyu Lin, Sean Tracy, Santiago Mercadal Vilchez, Kaitlyn Dykes, Timothy O'Connor, Mohamed Amin Ahmed, Vishal K Gupta, Abdullah Ladha, Stephanie Tsai, Jessica Taft Leonard, Ahmed Galal, Ryan Daniel Cassaday, Bijal D. Shah, Lori S. Muffly

Authors person Gregory Roloff University of Chicago, Chicago, IL info_outline Gregory Roloff, Rawan Faramand, Ibrahim Aldoss, Noam Edward Kopmar, Marc Schwartz, Simone E. Dekker, Chenyu Lin, Sean Tracy, Santiago Mercadal Vilchez, Kaitlyn Dykes, Timothy O'Connor, Mohamed Amin Ahmed, Vishal K Gupta, Abdullah Ladha, Stephanie Tsai, Jessica Taft Leonard, Ahmed Galal, Ryan Daniel Cassaday, Bijal D. Shah, Lori S. Muffly Organizations University of Chicago, Chicago, IL, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, City of Hope, Duarte, CA, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, University of Colorado Cancer Center, Aurora, CO, Oregon Health and Science University, Portland, OR, Duke Cancer Institute, Durham, NC, University of Minnesota, Minneapolis, MN, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, UC San Diego Health System, San Diego, CA, Loyola University Medical Center, Maywood, IL, Cedars-Sinai Medical Center, Los Angeles, CA, UCLA Medical Center, Los Angeles, CA, University of Southern California, Los Angeles, CA, Duke University, Durham, NC, University of Washington/Fred Hutchinson Cancer Center, Seattle, WA, H. Lee Moffitt Cancer Center, Tampa, FL, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA Abstract Disclosures Research Funding No funding received None. Background: In October 2021, brexucabtagene autoleucel (brexu-cel) became the first CAR-T cell therapy to receive FDA approval for adults (≥18 yrs) with relapsed/refractory (r/r) B-ALL. Approval was based on Phase II results of ZUMA-3, a single-arm, open-label, multicenter trial which reported on 55 treated patients with CR/CRi achieved in 71%; cytokine release syndrome (CRS) and neurologic toxicities occurred in 89% (grade 3-4, 24%) and 60% (grade 3-4, 25%), respectively. Here, we report outcomes of 76 adults with r/r B-ALL treated with post-approval brexu-cel at 13 U.S. centers. Methods: Retrospective data were collected across centers participating in a real-world outcomes collaborative of CAR-T in ALL (ROCCA). Descriptive statistics, Kaplan-Meier methodologies and cumulative incidence functions were used to summarize outcomes. Results: Among 76 patients infused, median age was 44 yrs (range, 18-81); 54% were male, 57% were non-Hispanic White (25% Hispanic), and 71% had Ph-neg disease. Median number of previous lines of therapy was 3.5 (range, 1-9) including blinatumomab in 53% and inotuzumab in 37%; 46% had relapsed post-transplant. Prior to apheresis, 69% of patients had active disease ( > 5% marrow blasts or presence of extramedullary disease), including 8 patients with CNS3 disease, 19% had detectable measurable residual disease (MRD) only, and 12% were MRD-neg. Median time from apheresis to infusion was 31 days. Lymphodepletion was predominantly with flu/cy (88%); 5 received cy/cladribine, and one patient each received single agent cy, single agent cladribine, and single agent bendamustine. Among 65 patients at least 28 days post-CAR-T with response assessed, 90.8% achieved CR/CRi, of whom 83% were MRD-neg, including CNS disease clearance in 7/8 CNS3 patients. CRS and ICANS (ASTCT criteria) occurred in 81.6% (grade 3-4, 6.6%) and 59% (grade 3-4, 38.6%), respectively. Median follow-up for survivors was 196.5 days (IQR 135.5-284.5). At last follow-up, 21 patients progressed/relapsed and 13 had died (7 of B-ALL; 6 of neurotoxicity/infection). Cumulative incidence of relapse and death in remission at 180 days were 31.5% (95% CI: 19.7%-44.1%) and 8.9% (95% CI: 3.5%-17.5%), respectively, while six-month PFS and OS were 58.8% (95% CI: 44.6%-70.5%) and 86.7% (95% CI: 75.8%-92.9%), respectively. Eleven patients underwent allogeneic transplant in CR/CRi after brexu-cel; all of whom remain in remission at last follow-up. Conclusions: These data are the first to demonstrate post-approval efficacy and toxicity rates of brexu-cel in adults with r/r B-ALL. Unlike the ZUMA-3 population, 31% of patients infused in this real-world cohort lacked morphologically detectable disease and 8 had CNS3 prior to apheresis. Our data confirm high response rates associated with brexu-cel in adult ALL, but also highlight the need for interventions to reduce associated toxicities.