Efficacy of chimeric antigen receptor T-cell therapy in diffuse large B-cell lymphoma (DLBCL): A meta-analysis.

Abstract

e19005 Background: Diffuse Large B- Cell Lymphoma (DLBCL) is an aggressive lymphoma; while R-CHOP has improved outcomes, 30-40% of patients often experiencing poor prognoses. CD19 CAR T-cell therapy has revolutionized treatment in this group but failure to achieve optimal outcomes in some patients prompted the development of dual target (CD19 & CD20) CAR T-cell therapy. Given the lack of recent comprehensive data on combined therapeutic outcomes, this meta analysis aims to evaluate the overall efficacy of CAR T-cell therapy in DLBCL. Methods: A systematic search of PubMed, Embase, and Cochrane databases identified 483 studies, from which 9 clinical trials (n=376) evaluating CAR T-cell therapy efficacy in DLBCL were included. Chang et al. (2018) reported efficacy of both single and dual target CAR T-cell therapy separately and they were included as separate data sets. Primary outcomes were pooled proportions of overall response rates (ORR) and complete response (CR) rates using random-effects models with 95% confidence intervals (CI). Results: A total of 376 patients across 9 studies were included. The median age ranged from 48 to 65 years across 7 studies. The median number of prior therapies were reported in six studies ranging from 2 to 5. The pooled proportion of ORR under a random-effects model was 0.74 (95% CI: 0.58–0.88). There was significant heterogeneity across the studies (I² = 84%, p < 0.0001), indicating considerable variability between the studies. Among the reported studies, the dual target CAR T-cell therapy studied in Chang et al. 2018 reported the highest response rate (0.91). All the ten studies reported complete response rates. The pooled proportion of CR was 0.45 (95% CI: 0.38–0.51) under the random-effects model. There was no significant evidence of between-study heterogeneity (I² = 6.9%, p = 0.38). Conclusions: This meta-analysis demonstrates that CAR T-cell therapy is an effective treatment for relapsed or refractory DLBCL, achieving a high pooled ORR of 74%, which was statistically significant despite high heterogeneity. While the CR rate was lower at 45%, the lack of significant heterogeneity in the CR results suggests consistent efficacy across different patient cohorts. These findings support the continued use and development of CAR T-cell therapies, with dual targeting approaches showing particular promise for improving clinical outcomes. Limitation: The generalizability of these findings may be constrained by the relatively small aggregate study population. Additionally, the pooled results may have been disproportionately influenced by a single large scale study (Kwon et al.), which possessed a significantly larger cohort compared to the other included trials.