The development of modern immune-based therapies for multiple myeloma has expanded rapidly over the past several years, and GPRC5D has been identified as a viable immunotherapeutic target. Herein, we discuss data and provide future perspectives on GPRC5D-directed CAR T cells and bispecific antibodies for patients with relapsed and/or refractory multiple myeloma.
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Mailankody, S. & Landgren, O. T-cell engagers — modern immune-based therapies for multiple myeloma. New Engl. J. Med. 387, 558–561 (2022).
Smith, E. L. et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci. Transl. Med. 11, eaau7746 (2019).
Pillarisetti, K. et al. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood 135, 1232–1243 (2020).
Mailankody, S. et al. GPRC5D-targeted CAR T cells for myeloma. New Engl. J. Med. 387, 1196–1206 (2022).
Bal, S. et al. Clinical activity of BMS-986393 (CC-95266), a G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T cell therapy, in patients with relapsed and/or refractory (R/R) multiple myeloma (MM): first results from a phase 1, multicenter, open-label study. Blood 140, 883–885 (2022).
Huang, H. et al. Phase I open-label single arm study of GPRC5D CAR T-cells (OriCAR-017) in patients with relapsed/refractory multiple myeloma (POLARIS). J. Clin. Oncol. 40, 8004–8004 (2022).
Chari, A. et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. New Engl. J. Med. 387, 2232–2244 (2022).
Carlo-Stella, C. et al. RG6234, a GPRC5DxCD3 T-cell engaging bispecific antibody, is highly active in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated intravenous (IV) and first subcutaneous (SC) results from a phase I dose-escalation study. Blood 140, 397–399 (2022).
Falchi, L., Vardhana, S. A. & Salles, G. A. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns and opportunities. Blood https://doi.org/10.1182/blood.2021011994 (2022).
Fernández de Larrea, C. et al. Defining an optimal dual-targeted CAR T-cell therapy approach simultaneously targeting BCMA and GPRC5D to prevent BCMA escape-driven relapse in multiple myeloma. Blood Cancer Discov. 1, 146–154 (2020).
K.N. and S.M. gratefully acknowledge the US National Cancer Institute Cancer Centre Support Grant (P30 CA008748) to Memorial Sloan Kettering Cancer Centre.
S.M. has acted as a consultant of Evicore, Janssen, Legend Biotech and Optum Oncology, receives honoraria from MJH Life sciences, Physician Education Resource and Plexus Education, and acknowledges research funding from Allogene Therapeutics Bristol Myers Squibb, Fate Therapeutics, Janssen Oncology, Juno Therapeutics and Takeda Oncology. K.N. and B.A.C. declare no competing interests.
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Nath, K., Costa, B.A. & Mailankody, S. GPRC5D as a novel immunotherapeutic target in multiple myeloma. Nat Rev Clin Oncol (2023). https://doi.org/10.1038/s41571-023-00735-4