Outcomes with non-BCMA CAR T cell therapy for multiple myeloma: A systematic review and meta-analysis.

e19541Background: Chimeric antigen receptor T cell therapy (CAR-T) has shown promise in treating multiple myeloma. Anti-BCMA CAR T cell therapy for MM has exhibited deep responses, but patients eventually get relapsed disease, which requires the need to explore non-BCMA targeted therapies. This meta-analysis aims to explore the non-BCMA CAR-T options for the MM patients. Methods: A systematic search was conducted on PubMed, Medline, and Embase following PRISMA guidelines and three studies reporting outcomes of non-BCMA CAR-T in MM patients were included after screening 1380 studies. Inter-study variance was assessed using the Der Simonian-Laird Estimator, and pooled analysis was conducted with 95% confidence intervals using the ‘meta’ package in R (version 4.16-2). Results: A total of 60 patients from three studies (2022-2023) were included in the analysis. The median age was 58 (38-76) years and the majority were male (60%, n=36). One study (33%) was phase II trial while the remaining two (67%) were phase I. All patients received GPRC5D-targeted CAR T cells. A median number of prior therapies was 5.8 (5.5-6) which included autologous transplantation (42%, n=25) and BCMA CAR T cell therapy (37%, n=22). High-risk cytogenetics was seen in 53% (n=32). Median follow-up time was 7.9 (5.2-10.1) months. The pooled rates of overall response rate (OR), complete response (CR), stringent complete response (SCR), very good partial response (VGPR), and partial response (PR) were 89.1% (95% CI 0.79-0.97, I²=64%, p=0.06, n=60), 24.1% (95% CI 0.14-0.36, I²=73%, p=0.03, n=60), 23.3% (95% CI 0.13-0.36, I²=89%, p<0.01, n=60), 18.7% (95% CI 0.09-0.30, I²=44%, p=0.17, n=60), and 10.2% (95% CI 0.03-0.20, I²=10%, p=0.33, n=60), respectively. The pooled rates of MRD negativity and mortality were 76.5% (95% CI 0.64-0.87, I²=83%, p<0.01, n=60) and 0.8% (95% CI 0.00-0.06, I²=0%, p=0.82, n=60). Median duration of response was 3.1 (0.5-5.1) months. Adverse events encountered were neutropenia (100%, n=60), anemia (85%, n=51), thrombocytopenia (80%, n=48), and cytokine release syndrome (42%, n=25). At 9 months, Zhang et al. reported a progression-free survival (PFS) of 87.5% (95% CI 38.7-98.1). Conclusions: GPRC5D can be an effective non-BCMA target for the treatment of myeloma. It has shown encouraging responses with tolerable side-effect profile. Further trials with new targets are required to understand the impact on survival and risk of relapse in the longer run.