Comparative efficacy and safety of CAR T-cell therapy versus standard of care for relapsed/refractory diffuse large B-cell lymphoma: A meta-analysis.

Abstract

e14526 Background: Diffuse large B-cell lymphoma (DLBCL) accounts for a third of all non-Hodgkin’s lymphomas. Many cases have been reported as refractory or relapsed despite the intensification of the standard chemoimmunotherapy. Emerging clinical trials are exploring CAR T-cell therapy to enhance survival outcomes in DLBCL after failed initial treatment. We evaluated the response and adverse events associated with CAR T-cell therapy compared to the standard of care (SOC) for DLBCL. Methods: Data was extracted from the eligible reports in PubMed, Google Scholar, Cochrane, Science Direct, and PlosOne. Three randomized controlled trials and three observational studies were included. The statistical analysis was run in random-effects model. The primary outcomes of interest were complete response (CR), partial response (PR), overall response (OR), stable disease (SD), and progressive disease (PD). The secondary outcomes were anemia, leukopenia, neutropenia, febrile neutropenia, thrombocytopenia, cytokine release syndrome (CRS), and neurotoxicity. Results: Overall, six studies with 1657 participants were eligible for the study, with 47.6% in the CAR T-cell therapy group and 52.4% in the SOC group. The median age was 59 years. CAR T-Cell therapy was reported to have higher odds of achieving complete response (OR: 2.07; 95% CI: 1.25, 3.42; I 2 = 81%; p = 0.004), partial response (OR: 1.43; 95% CI: 1.04, 1.96; I 2 = 31%; p = 0.03) and overall response (OR: 3.23; 95% CI: 1.78, 5.87; I 2 = 84%; p = 0.0001). CAR T-cell therapy was also found to have lower odds of achieving stable disease (OR: 0.37; 95% CI: 0.16, 0.89; I 2 = 78%; p = 0.03) and progressive disease (OR: 0.43; 95% CI: 0.20, 0.93; I 2 = 84%; p = 0.03) compared to SOC. Among the adverse events, neutropenia (OR: 3.34; 95% CI: 2.53, 4.41; I 2 = 0%; p < 0.00001), thrombocytopenia (OR: 0.45; 95% CI: 0.29, 0.72; I 2 = 62%; p = 0.0007) and neurotoxicity (OR: 9.50; 95% CI: 2.83, 31.94; I 2 = 31%; p = 0.0003) showed statistically significant differences between the CAR T-cell and SOC group. CAR T-cell therapy was also noted to have lower odds of developing febrile neutropenia (OR: 0.27; 95% CI: 0.09, 0.83; I 2 = 84%; p = 0.02). Anemia (OR: 0.60; 95% CI: 0.35, 1.05; I 2 = 67%; p = 0.07), and leukopenia (OR: 1.12; 95% CI: 0.69, 1.81; I 2 = 50%; p = 0.64) were not statistically significant. CRS was exclusive to the CAR T-cell group, with a proportion of 68.67%. No case was reported in the SOC group. Conclusions: CAR T-cell therapy offers the potential for improved outcomes with reduced risk of febrile neutropenia and thrombocytopenia in relapsed/refractory DLBCL. Significant adverse effects including neurotoxicity and cytokine release syndrome raise safety concerns and warrant further research to optimize the risk-benefit profile. Further studies are currently ongoing to assess its efficacy as a first-line treatment in DLBCL management.