CAR-T Cell Therapy Vs. Standard of Care for B-Cell Lymphoma: A Systematic Review and Meta- Analysis of Updated Results of Clinical Trials

Abstract

Background: For many years, platinum based immunochemotherapy followed by high dose chemotherapy and stem cell transplantation remained standard of care for relapsed/refractory large B-cell lymphoma. About half of the patients do not undergo transplantation due to disease insensitivity to 2 nd line therapy and cured in <30%. In recent years, feasibility of chimeric antigen receptor (CAR) t-cell therapies is tested as 2 nd line of treatment. In this meta-analysis, we will assess the efficacy and safety of CAR-T cell therapy as 2 nd line therapy as compared to standard therapy in large B cell lymphoma based on updated clinical trial results. Methods: A literature search was performed on PubMed and Embase with keywords for “CAR-T cell therapy” and “B-cell lymphoma” from the inception of data till 07/01/2023. PRISMA guidelines were followed while conducting this meta-analysis. A total of 3091 articles were screened and 3 randomized clinical trials (RCTs, N=865) were included based on inclusion criteria. “R” software was used to conduct this meta-analysis. Results: In 3 RCTs (N=865), 180 patients were treated with axicabtagene ciloleucel, 92 patients with lisocabtagene maraleucel, 162 patients with tisagenlecleucel, and 431 patients with standard therapy. Based on updated results of 2 trials (N=543), pooled hazard ratios (HRs) of progression free survival (PFS) was 0.47 (95% CI= 0.37-0.60, I 2=0), overall survival (OS) was 0.73 (95% CI=0.56-0.94, I 2=0), and event free survival (EFS) was 0.4 (95% CI=0.32-0.49, I 2=0) in favor of CAR-T cell therapy as compared to standard therapy. Pooled relative risk (RR) of complete response (CR) and overall response (ORR) were 1.88 (95% CI=1.57-2.25, I 2=2%), and 1.69 (95% CI=1.48-1.92, I 2=0%), respectively, in favor of CAR-T cell therapy. The Belinda RCT on tisagenlecleucel by Bishop et al. was the outlier. HR of EFS, RR of CR, and RR of ORR were 1.07 (95% CI= 0.82-1.4), 1.03 (0.73-1.47), and 1.09 (95% CI= 0.85-1.39), respectively, similar in the two groups. In 3 RCTs, RR of ≥ grade 3 any adverse effects were 1.02 (95% CI=0.92-1.12, I 2=72%), neurotoxicity was 7.35 (95% CI=0.97-55, I 2=64%), and neutropenia was 1.41 (95% CI=1.04-1.91, I 2=78%). Pooled incidence of ≥ grade cytokine release syndrome (CRS) was 5% (CI=0.03-0.08) and was 0 with standard therapy. Fig 1. Conclusion: Based on updated results, CAR-T cell therapies, axicabtagene ciloleucel and lisocabtagene maraleucel, were significantly more effective in terms of response and survival rates. ≥Grade 3 side effects were similar with CAR-T cell and standard therapy. CRS, neurotoxicity, and hematological side effects were higher with CAR-T cells. Tisagenlecleucel was found as an outlier and the efficacy was similar to standard care. More randomized double-blind large-scale phase III clinical trials are needed to confirm these results.