Abstract
Introduction: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment that induces high remission rates in relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Despite these initial responses, the durability of remission remains uncertain, as many patients ultimately relapse. This challenge underscores the need to optimize post-CAR T-cell management strategies aimed at sustaining long-term disease control. Allogeneic hematopoietic stem cell transplant (allo-HSCT) remains a well-established curative approach in the pursuit of durable remission for patients with high-risk ALL. However, real-world comparative data evaluating outcomes between patients who undergo consolidation allo-HSCT versus those who do not after CAR T-cell therapy for R/R disease are limited, and existing evidence is largely derived from small retrospective cohorts or single-institution experiences. To address this gap, we conducted a large-scale, real-world analysis to compare survival and remission outcomes following CAR T-cell therapy for R/R ALL with or without subsequent allo-HSCT.
Methods: We utilized the TriNetX Global Federated Research Network, which aggregates de-identified electronic medical data from more than 120 healthcare networks worldwide. A retrospective cohort analysis was completed for patients with R/R ALL who subsequently underwent CAR T-cell therapy who either did (HSCT+) or did not (HSCT-) proceed to consolidation allo-HSCT. Screened cohorts were subjected to propensity score matching (PSM) to limit confounders and mediators of outcomes. The primary outcome was 5-year overall survival (OS) and the secondary outcome was the proportion of patients remaining in remission at 5 years following CAR T-cell therapy.
Results: Initial screening yielded 239 patients in the HSCT+ cohort and 198 patients in the HSCT- cohort. Following PSM, 122 patients remained in each arm, with balanced baseline characteristics across demographic and disease variables. Median follow-up was 508 days for HSCT+ and 353 days for HSCT-. HSCT+ was associated with significantly improved 5-year OS (5-year Kaplan-Meier estimates: 59.5% for HSCT+ vs. 55.9% for HSCT-; HR = 0.594, 95% CI: 0.375-0.939; P = 0.0172). Additionally, a higher percentage of patients in the HSCT+ group remained in remission at the 5-year time point following CAR T-cell therapy (79.5% for HSCT+ vs. 55.7% for HSCT-; risk difference 23.8%, 95% CI: 12.4%-35.1%; P < 0.0001).
Conclusions: In this real-world, propensity score matched analysis, consolidation allo-HSCT following CAR T-cell therapy for R/R ALL was associated with improved 5-year overall survival and a higher proportion of patients remaining in remission at 5 years compared with non-transplant consolidation strategies. These findings highlight the potential role of allo-HSCT in sustaining the long-term benefit of CAR T-cell therapy for R/R ALL. Large-scale prospective studies are needed to further validate these results and guide management of patients with post-CAR T-cell therapy R/R ALL.
