A G protein-coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy led to a 71% response rate in patients with heavily pretreated multiple myeloma.
Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center, and colleagues conducted the phase I dose-escalation study of the GPRC5D-targeted CAR-T therapy because previous research identified GPRC5D as an immunotherapeutic target in patients with multiple myeloma.
They performed the research because B-cell maturation antigen (BCMA)-targeted CAR T-cell therapies “have generated responses in patients with advanced myeloma, but relapses are common” and “preclinical studies have shown the efficacy of GPRC5D-targeted CAR T-cells, including activity in a BCMA antigen escape model,” Dr. Mailankody and colleagues wrote.
The researchers administered the GPRC5D-targeted CAR T-cell therapy, MCARH109, at four dose levels to 17 patients with heavily pretreated multiple myeloma, including patients who relapsed after BCMA therapies.
The maximum tolerated dose of MCARH109 was 150 × 106 CAR T-cells, as one patient who received the 450 × 106 dose had grade 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and two patients treated with that dose had grade 3 cerebellar disorder of unclear cause.
None of the 12 patients treated with doses ranging from 25 × 106 to 150 × 106 CAR T-cells had cerebellar disorders, immune effector cell-associated neurotoxicity syndrome of any grade, or grade 3 or higher cytokine release syndrome.
The response rate was 71% in the entire cohort of patients, while it was 58% in patients receiving doses ranging from 25 × 106 to 150 × 106 CAR T-cells. Patients who previously received BCMA therapies had a 70% response rate, while they had a 50% response rate when treated with doses ranging from 25 × 106 to 150 × 106 CAR T-cells.
“The results of this study of a GPRC5D-targeted CAR T-cell therapy (MCARH109) confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma,” Dr. Mailankody and colleagues concluded.
Mailankody S, Devlin SM, Landa J, et al. GPRC5D-targeted CAR T cells for myeloma. N Engl J Med. 2022;387(13):1196-1206. doi:10.1056/NEJMoa2209900