Allogeneic Hematopoietic Cell Transplant Following Standard of Care Brexucabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia: Results from the Real-World Outcomes Collaborative of Chimeric Antigen Receptor T in Adult Acute Lymphoblastic Leukemia.

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Despite encouraging outcomes, the majority of adults relapse following brexu-cel, highlighting the need for strategies to improve the durability of response. One such strategy is consolidative allogeneic stem cell transplant (alloHCT). Here, we report outcomes of adults with B-ALL who underwent consolidative alloHCT following commercial brexu-cel as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA). We performed a retrospective multicenter analysis of adults with R/R B-ALL who underwent consolidative alloHCT in complete remission after commercial brexu-cel and were registered in ROCCA. ROCCA includes 41 US institutions contributing retrospective data for adults with B-ALL treated with brexu-cel between 2021 and 2025. Patients who received alloHCT after CAR T failure were excluded. Primary endpoints were 12-mo overall survival (OS) and event-free survival (EFS); secondary endpoints included relapse, non-relapse mortality (NRM), and graft-versus-host disease (GVHD). Among 399 brexu-cel-treated patients, 65 underwent consolidative alloHCT, including 56 patients who underwent a first alloHCT and nine who underwent second alloHCT. Among recipients of first alloHCT, the median age was 34 yr, and patients were heavily pretreated with a median of three prior lines of therapy. With a median follow-up of 11 mo post-HCT, the estimated 1-yr post-HCT OS and EFS were 79% (95% CI, 64 to 88) and 66% (95% CI, 51 to 77), respectively. The 1-yr cumulative incidence (CI) of relapse was 19%, and NRM was 13%. Acute grade II to IV GVHD occurred in 18%, grade III to IV in 4%, and moderate-to-severe chronic GVHD in 12%. In univariable analysis, age ≥40 was associated with inferior OS (HR 4.31, 95% CI 1.40 to 13.3) and EFS (HR 3.36, 95% CI 1.43 to 7.91), whereas myeloablative conditioning was associated with improved EFS (HR 0.37, 95% CI 0.15 to 0.93). Among second alloHCT recipients, 1-yr EFS and OS were 59% (95% CI, 19 to 85). The 1-yr CI NRM was 41% and there were no relapses documented among these patients. In this large real-world cohort, consolidative alloHCT after brexu-cel was feasible and associated with encouraging survival, low relapse rates, and acceptable toxicity, particularly among HCT-naive recipients. These findings support alloHCT as a viable consolidation strategy following CAR T-induced remission and highlight the need for prospective studies to refine patient selection, conditioning regimens and transplant approaches in the post-CAR T setting.

Duke Scholars

Author Chenyu Lin Medicine, Hematologic Malignancies and Cellular Therapy