CAR T-cell therapy as a bridge to second allo-HSCT in relapsed B-ALL

Results from a single-center retrospective analysis comparing outcomes by bridging strategy in adults with B-cell acute lymphoblastic leukemia (B-ALL) who had relapsed after a first allogeneic stem cell transplantation (HSCT1) and subsequently underwent a second allo-HSCT (HSCT2) in complete remission (CR) between 2015 and 2025 were published in Transplantation and Cellular Therapy by Agrawal et al. The primary outcome was progression-free survival (PFS). 

Key data: Among 55 patients, 23 received chimeric antigen receptor (CAR) T-cell therapy as immediate pre-HSCT2 treatment and 32 received other salvage therapies, including blinatumomab (n = 12) and inotuzumab ozogamicin (n = 12). At a median follow-up of 44.6 months for the overall cohort, 2-year PFS was 67.6% with CAR T-cell bridging vs 31.4% with other salvage therapies (p = 0.002) and 2-year overall survival (OS) was 77.3% vs 51.6%, respectively (p = 0.021). In multivariable analysis, CAR T-cell therapy remained independently associated with superior PFS (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11–0.62; p = 0.002) and OS (HR, 0.33; 95% CI, 0.13–0.88; p = 0.026). 

Key learning: In this analysis, bridging with CAR T-cell therapy before HSCT2 was associated with significantly improved survival outcomes vs other salvage approaches in adults with B-ALL who relapsed after HSCT1 in CR. These findings suggest CAR T-cell therapy may be an effective bridge to HSCT2; however, prospective multicenter studies are needed to define optimal patient selection and transplant timing.