The fully human anti-GPRC5D CAR T-cell therapy RD118 induces durable remissions in relapsed/refractory multiple myeloma
Abstract
Abstract GPRC5D has emerged as a promising therapeutic target in relapsed/refractory multiple myeloma (R/R MM), particularly following progression after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapies. RD118 is a novel CAR-T therapy incorporating a fully human single-domain antibody fragment targeting GPRC5D. In this phase 1 study, 18 R/R patients (17 with MM and 1 with a history of primary plasma cell leukemia) received a single infusion of RD118 at 1.0 × 106, 2.0 × 106, or 3.0 × 106 CAR+ T cells per kg. At a median follow-up of 17.0 months, the overall response rate (ORR) was 94.4%, including 72.2% complete or stringent complete responses. Among the 7 patients previously exposed to BCMA-directed CAR-T therapy, ORR reached 85.7%. Median progression-free survival (PFS) was 18.2 months (95% confidence interval, 14.4 to not estimable), with 12-month PFS and overall survival rates of 82.1% and 93.3%, respectively. Cytokine release syndrome occurred in 88.9% of the patients, primarily grade 1 to 2. One patient developed grade 3 immune effector cell–associated neurotoxicity, which resolved within 72 hours. No cerebellar toxicities or treatment-related deaths were reported. These findings support that RD118 is a highly effective and safe therapeutic option for heavily pretreated R/R MM. This trial was registered at www.clinicaltrials.gov as #NCT05759793 and #NCT05219721.
Article Details
Authors (17)
Mengmeng Pan
Di Wang
Jie Xu
Shiwei Jin
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yan Wang
Yi Tao
Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental Safety, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, China.
Yuanfang Liu
Key Laboratory of Biomedical Polymers-Ministry of Education, College of Chemistry and Molecular Sciences
Wanyan Ouyang
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xiangqin Weng
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hongmei Yi
4Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yu Huang
Xinmei Cao
5Nanjing IASO Biotechnology Co, Ltd, Nanjing, China
Shuhua Li
Fuyuan Zhang
Weiping Zhang
Chunrui Li
3Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Jian-Qing Mi
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Research Unit of Hematologic Malignancies Genomics and Translational Research of Chinese Academy of Medical Sciences, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine