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Updated: Jan 14, 2026
Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
The fully human anti-GPRC5D CAR T-cell therapy RD118 induces durable remissions in relapsed/refractory multiple
Mengmeng Pan1,2, Di Wang3, Jie Xu1,2
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.
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.
Insights
RD118, a new CAR T-cell therapy targeting GPRC5D, shows high effectiveness in relapsed/refractory multiple myeloma patients. It achieved a 94.4% overall response rate with durable survival outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Hematology
Background:
- Relapsed/refractory multiple myeloma (RRMM) presents a significant unmet need, especially after BCMA-directed CAR T-cell therapy.
- GPRC5D is an emerging therapeutic target in RRMM, offering a potential alternative or sequential treatment strategy.
Purpose of the Study:
- To evaluate the safety and efficacy of RD118, a novel GPRC5D-targeting CAR T-cell therapy, in patients with RRMM.
- To assess response rates, progression-free survival (PFS), and overall survival (OS) in this patient population.
Main Methods:
- A phase 1 clinical trial involving 18 patients with RRMM (17 multiple myeloma, 1 primary plasma cell leukemia).
- Patients received a single infusion of RD118 at escalating doses (1.0, 2.0, or 3.0 × 10^6 CAR+ T cells/kg).
- Median follow-up was 17.0 months.
Main Results:
- An overall response rate (ORR) of 94.4% was observed, with 72.2% achieving complete or stringent complete responses.
- Among patients previously treated with BCMA-directed CAR T-cell therapy (n=7), the ORR was 85.7%.
- Median PFS was 18.2 months, with 12-month PFS and OS rates of 82.1% and 93.3%, respectively. Cytokine release syndrome (CRS) occurred in 88.9% (mostly grade 1-2); one grade 3 ICANS resolved within 72 hours.
Conclusions:
- RD118 demonstrates high efficacy and a manageable safety profile in heavily pretreated RRMM patients.
- This GPRC5D-targeting CAR T-cell therapy represents a promising option for patients progressing after BCMA-directed therapies.
- Further investigation in larger trials is warranted to confirm these findings.
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