Promising Clinical Efficacy for GPRC5D-Targeting CAR-T Cell Therapy in R/R Multiple Myeloma

According to a phase 2, single-arm study, anti-GPRC5D CAR-T cell therapy provided a promising clinical efficacy and manageable safety profile in patients with relapsed/refractory (R/R) multiple myeloma.

Eligible patients included those aged 18 to 70 years with R/R multiple myeloma. Lymphodepletion was performed before patients received 2 × 106/kg anti-GPRC5D CAR-T cells. The primary endpoint in this study was the proportion of patients who achieved an overall response. It was also noted that safety was evaluated in eligible trial participants.

From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR-T cells. When response was measured at a median follow-up of 5.2 months (range, 3.2-8.9), the overall response rate was 91% (95% confidence interval [CI], 76 to 98; 30 of 33 patients). This included 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 all 9 patients with previous anti-B-cell maturation antigen (BCMA) CAR-T cell therapy, which included 2 patients who had received repeated anti-BCMA CAR-T cell infusions with no responses at the previous time. 

Reported adverse events included grade 3 or higher hematologic toxicities of neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Additionally, grade 1 or 2 cytokine release syndrome occurred in 25 (76%) of 33 patients, and neurotoxicities occurred in 3 patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache).

Jieyun Xia, MD, and colleagues concluded, “For patients with [multiple myeloma] 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.”

Source:

Xia J, Li H, Yan Z, et al. Anti-G protein-coupled receptor, class C group 5 member D chimeric antigen receptor T cells in patients with relapsed or refractory multiple myeloma: A single-arm, phase II trial. Journal of Clinical Oncology. March 7, 2023. doi: 10.1200/JCO.22.01824