GPRC5D-Targeted CAR T-Cell Therapy Demonstrates Efficacy and Safety for Patients With R/R MM

Among patients heavily pretreated for relapsed/refractory (R/R) multiple myeloma (MM), G protein-coupled receptor, class C, group 5, and member D (GPRC5D)-targeted CAR T-cell therapy was found to be effective and tolerable, according to results from systematic meta-analysis published in Anti-Cancer Agents in Medicinal Chemistry.

Previous research has found an overexpression of GPRC5D is associated with genetic abnormities and plasma cell load within human tissue. Anti-GPRC5D CAR T-cells have demonstrated improvement among patients with MM as a target antigen therapy. Researchers conducted a systematic review and meta-analysis to determine the safety and efficacy of GPRC5D-targeted CAR T-cell therapy.

The primary outcome was efficacy of GPRC5D-targeted CAR T-cell therapy, determined by overall response rate (ORR) and complete response (CR) rate. Secondary outcomes were adverse events including hematologic toxicities, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS).

Among 130 patients within 4 evaluable studies, the median age rage was 58 to 64 and majority of patients were diagnosed with R/R MM and/or heavily pretreated. Across all included studies, the median lines of therapy received by patients ranged from 4 to 6. 

The ORR among all patients was 87% (95% confidence interval [CI], 81 to 93). Patients with prior BCMA-targeted therapy (74%; 95% CI, 65 to 73) had a lower response than patients without prior BCMA-targeted therapy (88%; 95% CI, 79 to 99). The CR rate was 48% (95% CI, 33 to 63), with a partial response reported in 25% (95% CI, -4 to 54). Minimal residual disease negativity was achieved by 65% (95% CI, 33 to 96) of patients with R/R MM treated with GPRC5D-targeted CAR T-Cell therapy.

In terms of safety, the most common adverse event was CRS which occurred in 83% of patients (95% CI, 76 to 90) with 5% (95% CI, 1 to 10) being grade 3 or higher. Hematologic toxicities including anemia at any grade was reported by 86% of patients (95% CI, 73 to 99), with grade 3 or higher anemia occurring in 46% of patients (95% CI, 30 to 61).

Report of neurologic adverse events were headache (10%; 95% CI, 0 to 19), dizziness (8%; 95% CI, 2 to 14), ICANS at any grade (8%; 95% CI, 3 to 13), and ICANS grade 3 or higher (3%; 95% CI, 0 to 6). Dermatologic adverse events included skin changes (19%; 95% CI, 6 to 32), pruritis (8%; 95% CI, 2 to 19), and changes to nails (33%; 95% CI, 12 to 54).

“Our meta-analysis has shown anti-GPRC5D CAR T cells to be safe and active in the treatment of heavily pretreated patients with R/R MM or limited with other therapeutic options,” the researchers concluded, adding,  “the current stage of CAR-T therapy for MM is still in its early phases, and further investigation is required to gain a deeper understanding of the underlying mechanisms involved.”

Source:

Robat-Jazi B, Mahalleh M, Dashti M, et al. A systematic review and meta-analysis on the safety and efficacy of CAR T Cell therapy targeting GPRC5D in patients with multiple myeloma: a new insight in cancer immunotherapy. Anti-cancer agents in medicinal chemistry. Published online January 30, 2025. doi: 10.2174/0118715206350342241224073809