Related Experiment Video
Updated: Aug 7, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed
Jieyun Xia1,2,3, Hujun Li1,2,3, Zhiling Yan1,2,3
1Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Purpose:
G protein-coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM.
Methods:
This phase Ⅱ, single-arm study enrolled patients (18-70 years) with R/R MM. Lymphodepletion was performed before patients received 2 × 106/kg anti-GPRC5D CAR T cells. The primary end point was the proportion of patients who achieved an overall response. Safety was also evaluated in eligible patients.
Results:
From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2-8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses. Partial responses or better were observed in nine (100%) of nine patients with previous anti-B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache).
Conclusion:
Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM. For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.
Insights
Anti-GPRC5D CAR T-cell therapy demonstrated high efficacy in relapsed or refractory multiple myeloma (MM), with a 91% overall response rate. This immunotherapy offers a promising alternative for patients who have exhausted other treatment options.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Multiple myeloma (MM) is a hematologic malignancy with limited treatment options for relapsed or refractory (R/R) cases.
- G protein-coupled receptor, class C group 5 member D (GPRC5D) is identified as a potential surface target for MM immunotherapy.
- Chimeric antigen receptor (CAR) T-cell therapy has emerged as a powerful tool in cancer treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of anti-GPRC5D CAR T-cell therapy in patients with R/R MM.
- To determine the overall response rate (ORR) as the primary endpoint.
- To assess the safety profile, including adverse events and toxicities.
Main Methods:
- A phase II, single-arm clinical study was conducted.
- Eligible patients with R/R MM received anti-GPRC5D CAR T-cells after lymphodepletion.
- The primary endpoint was the ORR, with safety evaluated concurrently.
Main Results:
- 33 patients with R/R MM were infused with anti-GPRC5D CAR T-cells.
- An overall response rate of 91% was observed, with 33% achieving stringent complete responses.
- In patients previously treated with anti-BCMA CAR T-cells, 100% achieved partial responses or better. Grade 3 or higher toxicities included neutropenia (100%), anemia (52%), and thrombocytopenia (45%). Cytokine release syndrome occurred in 76% (all grade 1 or 2), and neurotoxicity in 3 patients.
Conclusions:
- Anti-GPRC5D CAR T-cell therapy exhibits significant clinical efficacy in R/R MM patients.
- The safety profile of this therapy is manageable.
- This CAR T-cell approach represents a potential alternative for MM patients refractory to or progressed after anti-BCMA CAR T-cell therapy.
