Efficacy of CAR-T cell therapy versus allogeneic stem cell transplantation in relapsed/refractory B-acute lymphoblastic leukemia: A systematic review of 12 clinical trials.

Abstract

e18533 Background: Relapsed/Refractory B- Acute Lymphoblastic Leukemia poses a significant challenge in treatment and is often associated with poorer prognosis. Allogenic Hematopoietic Stem Cell Transplantation (HSCT) used to be the primary salvage therapy but is often associated with a significantly increased risk of adverse effects. In recent years, Chimeric Antigen Receptor T- Cell (CAR-T) therapy has emerged as a new treatment approach in the management of Relapsed/Refractory B- ALL. This systematic review aims to compare CAR-T therapy's and HSCT's efficacy in relapsed/refractory ALL patients. Methods: We conducted a search across databases, including PubMed, Clinicaltrials.gov, and Google Scholar. We reviewed clinical trials up to the year 2025. A total of 1655 articles were screened. Duplicated articles and those meeting the Exclusion criteria were excluded. 12 Clinical trials were selected for analysis after they met the inclusion criteria. Efficacy assessment was done using primary endpoints of Combined Complete Remission, Median Relapse Free Survival, and Median Overall Survival. PRISMA guidelines were followed in writing this systematic review. Results: A total of 437 patients diagnosed with r/r B-ALL were treated with CAR-T Cell Therapy. The combined complete remission (CR) rate for this group was 74% (n=323.5). The cumulative median relapse-free survival (RFS) varied from 1.6 months to 12 months, with a median RFS of 7.3 months, IQR: 6.93-7.6. The median overall survival (OS) was noted to be 16 months, with Q1(25th percentile):12.91, and Q3 (75th percentile):19.1, IQR=12.91-19.1 months. A total of 242 patients were treated with HSCT, achieving a combined complete remission (CR) of 88%. The median RFS was 7.7 months and the median overall survival (OS) was 9 months for this group. CAR-T Cell Therapy is associated with a distinctive side effect profile, primarily including cytokine release syndrome (CRS, CAR-T cell-associated neurotoxicity and immune effector cell-associated neurotoxicity syndrome (ICANS) are significant concerns. In contrast, HSCT predominantly poses the risk of graft-versus-host disease (GVHD). Conclusions: CAR-T cell therapy presents a compelling option for patients with r/r B-ALL. It is associated with a significant durability of the response and adverse effects which are better manageable. Whereas HSCT’s strong efficacy can be a treatment option for this high-risk population. Patients who had a relapse after CAR-T received HSCT and relapse after HSCT received CAR-T as an option, both led to better clinical outcomes. Further research is essential to define the best approaches in utilizing these treatments synergistically. Understanding these potential risks is also crucial in making informed treatment decisions and in developing strategies to mitigate side effects effectively.