A new fully human CAR-T cell therapy targeting GPRC5D has demonstrated remarkable clinical results in treating relapsed or refractory multiple myeloma (R/R MM), with findings recently published in the top-tier hematology journal Blood.
The Phase I open-label, dose-escalation study evaluated the safety and efficacy of the investigational product RD118 in heavily pretreated patients. Conducted by Ruijin Hospital of Shanghai Jiao Tong University and Tongji Hospital of Huazhong University of Science and Technology, the study included 18 patients—17 with R/R MM and one with relapsed primary plasma cell leukemia (pPCL). Participants had a median age of 59.5 years and had undergone a median of five prior therapy lines, with many showing high-risk and multi-drug resistant features.
At a median follow-up of 17 months, RD118 achieved an overall response rate (ORR) of 94.4%, with 72.2% of patients reaching complete or stringent complete remission (CR/sCR). Even among patients previously treated with BCMA-targeted CAR-T therapies, the ORR remained 85.7%, and 71.4% achieved CR/sCR. The median progression-free survival (PFS) reached 18.2 months, with 12-month PFS and overall survival rates of 82.1% and 93.3%, respectively.
The therapy showed a manageable safety profile. Cytokine release syndrome (CRS) occurred in 88.9% of patients, mostly grade 1–2, and only one grade ≥3 case was reported and resolved quickly. One patient experienced grade 3 ICANS, which fully resolved within 72 hours. No treatment-related deaths or cerebellar toxicity were reported.
Experts noted that GPRC5D, as a novel target independent of BCMA, could overcome resistance and antigen escape seen in existing CAR-T therapies. The use of a fully human nanobody (VHH) design and a 4-1BB/CD3ζ signaling domain may enhance durability, reduce immunogenicity, and improve safety—marking a major step forward for next-generation CAR-T therapies in multiple myeloma.
