Long-term outcomes of CAR-T cell therapy in DLBCL.

Abstract

e19004 Background: CAR T-cell therapy, which involves engineering a patient's T-cells with a chimeric antigen receptor (CAR) to target and eliminate cancer cells, has revolutionized treatment for hematological malignancies By bypassing MHC restrictions ,CAR T-cells effectively target antigens such as CD19 and BCMA, achieving high response rates even in relapsed/refractory cases However, challenges such as severe toxicities (cytokine release syndrome, neurotoxicity) prolonged cytopenias, high costs and limited accessibility persist. Methods: A systematic review and meta-analysis evaluated CAR T-cell therapy in relapsed/refractory aggressive B-cell lymphoma, adhering to PRISMA guidelines. PubMed, Embase, Cochrane Library and clinical trial registries identified 27 studies. Eligible studies included randomized controlled trials, cohort studies, and clinical trials reporting overall survival (OS), progression-free survival (PFS) response rates, and adverse events Four reviewers extracted data and assessed bias using the Cochrane tool. Statistical analyses included Cox Proportional Hazards models and Kaplan-Meier survival estimates. Limitations included dataset imbalance (n = 27; p = 345) affecting generalizability. Results: Survival outcomes: Median OS was 15.6 months (95% CI: 13.1–18.7), with 2- and 1-year survival rates of 45% and 65% respectively. Median PFS was 12.2 months (95% CI: 10.4–14.8). Efficacy: Complete remission occurred in 59% with a median response duration of 8.3 months. Safety profile: CRS occurred in 100% of patients, with severe cases (Grade 3–4) in 50% mild to moderate 40.6% and fatal CRS in 9.37%. Neurotoxicity affected 22%, resolving in 2.1 months. Late-onset cytopenias occurred in 37%, resolving in 6.8 months. Re-hospitalization for toxicity management occurred in 26.3%. Quality-of-life analysis revealed significant improvements in emotional and physical well-being. Exploratory analyses showed no significant age impact on OS or PFS but poorer survival was observed in patients with secondary malignancies (HR = 1.82, 95% CI: 1.21–2.75, p = 0.008). Conclusions: This systematic review underscore the significant long-term benefits and challenges of CD19 CAR-T cell therapy for diffuse large B-cell lymphoma (DLBCL). The therapy demonstrates a promising outcome, achieving durable remissions and high response rates in heavily pretreated patients. Toxicities, including cytokine release syndrome (CRS) and neurotoxicity, remain substantial but largely manageable, with most late-onset toxicities resolving within 6.8 months. These findings highlight the transformative potential of CD19 CAR-T therapy as a durable treatment option for relapsed or refractory DLBCL. However, improved toxicity management and long-term follow-up protocols are essential to optimize outcomes and address relapse risks. CRS Grade Frequency Percentage Mild to Moderate (Grade A) 13 40.63% Severe (Grade B) 16 50.00% Fatal (Grade C) 3 9.37%