Anti-GPRC5D CAR T-Cell Therapy for Patients With R/R MM

Results from a Phase 2 Clinical Trial

According to findings from a phase 2 clinical trial recently published in the Journal of Clinical Oncology, anti-G protein-coupled receptor, class C group 5-member (GPRC5D) chimeric antigen receptor (CAR) T-cell therapy yielded effective and safe outcomes among patients with relapsed/refractory (R/R) multiple myeloma (MM), including those who had previously undergone anti-B-cell maturation antigen (BCMA) CAR T-cell therapy.

According to Jieyun Xia, MD, Xuzhou Medical University, Xuzhou, China, et al, “relapses with diminished or altered surface expression of BCMA are increasingly recognized as a frequent cause of treatment failure, whereas BCMA is expressed in essentially all cases of MM at clinical presentation. BCMA escape could limit the potential of CAR T-cell therapy to deliver durable responses.” 

There has also been prior evidence that the overexpression of GPRC5D, a type C 7-pass transmembrane receptor protein, was associated with poor outcomes in patients with MM, such as plasma cell burden and genetic aberrations. 

Because of this, the study authors looked to test anti-GPRC5D CAR T-cell therapy for efficacy and safety among patients with R/R MM, particularly those who had undergone anti-BCMA CAR T-cell therapy previously. The primary endpoint was the overall response, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR). The secondary endpoint was the evaluation of safety. 

33 patients with R/R MM and a median age of 58 years were enrolled in this study and administered 2 × 106/kg/kg anti-GPRC5D CAR T-cells. A lymphodepletion regimen, using fludarabine and cyclophosphamide, was performed prior to treatment. 

At a median follow-up of 5.2 months, the overall response was 91% (n=30), including a 33% (n=11) sCR, 30% (n=10) CR, 12% (n=4) VGPR, and 15% (n=5) PR. 100% (n=9) of patients who had undergone previous anti-BCMA CAR T-cell therapy achieved a partial response or greater. 

In terms of safety, the most commonly occurring hematologic malignancies ≥ grade 3 were neutropenia (n=33), anemia (n=17), and thrombocytopenia (n=15). Cytokine release syndrome of grade 1 or 2 was observed in 76% of patients (n=25). 

As all endpoints were met, Dr Xia et al concluded, “Anti-GPRC5D CAR T cells might be a very potential candidate treatment for patients with MM progressed after anti-BCMA CAR T-cell therapy or refractory to anti-BCMA CAR T-cells.”

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. J Clin Oncol. 2023;41(14):2583-2593. doi:10.1200/JCO.22.01824