A Systematic Review and Meta-analysis on the Safety and Efficacy of CAR T Cell Therapy Targeting GPRC5D in Patients with Multiple Myeloma: A New Insight in Cancer Immunotherapy.

Background: Despite ongoing advances and introducing innovative therapeutic approaches for the treatment of multiple myeloma (MM), relapses are common, with low overall survival rates. G protein-coupled receptor, class C, group 5, and member D (GPRC5D) has been expressed in several myeloma cell lines and has demonstrated encouraging outcomes results in in-vitro studies as a potential target for immunotherapies.

Objective: We aimed to investigate the safety and efficacy of GPRC5D-targeted CAR T cell therapies in MM patients.

Methods: On August 24, 2023, the databases of PubMed, Scopus, Embase, and Web of Science were systematically searched for pertinent studies. After completing a two-step title/abstract and full-text screening process, the eligible studies were included.

Results: Following the screening of 107 articles, four studies of 130 multiple myeloma patients treated with GPRC5D-targeted CAR T-cell therapy were included. The meta-analyses showed an ORR of 87% (95% CI [81- 93%]), with 74% (95% CI [65-73%]) for those with prior BCMA-targeted therapy and 88% (95% CI [78-99%]) for those without. PR was 25%, VGPR 33%, and CR/sCR 48%, with 65% achieving MRD-negativity. In terms of safety, hematologic AEs were common, with anemia reported in 86% of patients. Non-hematologic common AEs included CRS (83%, 5% grade ≥3) and hypocalcemia (63%, 10% grade ≥3). No significant publication bias was detected.

Conclusion: GPRC5D is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (R/R) MM and heavily pretreated patients.