Application of CAR-T cell therapy in B-cell lymphoma: a meta-analysis of randomized controlled trials

Abstract

Background: This study aims to compare the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) immunotherapy with standard treatment for B-cell lymphoma, providing evidence-based support for the more efficient use of CAR-T cell immunotherapy.

Methods: We conducted a comprehensive literature search of high-quality randomized controlled trials (RCTs) on CAR-T therapy for B-cell lymphoma in the following databases: Wanfang, Web of Science, CNKI, VIP database, and PubMed, up to February 2024. The outcome measures included objective remission rate (ORR), complete remission rate (CRR), and incidence of adverse reactions. Subgroup analysis was performed based on the differences in co-stimulatory domains. Meta-analysis was conducted using Review Manager 5.4 and Stata software.

Results: A total of five RCTs involving 1670 patients were included in this meta-analysis. The results showed that the CAR-T treatment group had significantly higher ORR (RR: 1.47, 95% CI 1.23-1.76, I² = 80%, p < 0.0001), CRR (RR: 2.19, 95% CI 2.16-3.79, I² = 93%, p = 0.005), cytokine release syndrome (CRS) incidence (RR: 34.51, 95% CI 2.27-523.78, I² = 98%, p = 0.01), neurotoxicity (NT) incidence (RR: 6.00, 95% CI 1.82-19.75, I² = 80%, p = 0.003), neutropenia incidence (RR: 1.39, 95% CI 1.02-1.88, I² = 93%, p = 0.03), leukopenia incidence (RR: 1.39, 95% CI 1.04-1.87, I² = 61%, p = 0.03), and headache incidence (RR: 1.56, 95% CI 1.25-1.95, I² = 34%, p < 0.0001) compared to the standard treatment group. Subgroup analysis based on co-stimulatory domains revealed that the 4-1BB subgroup had higher incidences of CRR, CRS, NT and leukopenia than the CD28 subgroup; however, the CD28 subgroup exhibited higher ORR and neutropenia than the 4-1BB subgroup.

Conclusion: CAR-T cell immunotherapy demonstrates superior efficacy compared to standard therapy in treating B-cell lymphoma. However, CAR-T treatment can lead to adverse reactions such as CRS and NT. Infusion of an appropriate dose of CAR-T cells (e.g., 100 × 10⁶) may be a strategy to mitigate the risk of CRS and NT.

Keywords: Adverse reaction; B-cell lymphoma; CAR-T cell immunotherapy; Efficacy; Meta-analysis.