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GPRC5D as a novel immunotherapeutic target in multiple myeloma

Nature Reviews Clinical Oncology volume 20, pages 281–282 (2023)Cite this article

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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.

T-cell-engaging therapies directed at B cell maturation antigen (BCMA) — including chimeric antigen receptor (CAR) T cells and bispecific antibodies — are changing the natural history of patients with triple-class-exposed relapsed and/or refractory multiple myeloma (MM) (after disease progression on an immunomodulatory drug, proteasome inhibitor and anti-CD38 monoclonal antibody), with several FDA-approved products now available1. However, most patients are likely to eventually have disease relapse on such therapies and additional immunotherapeutic options are much needed. G-protein-coupled receptor, class C, group 5, member D (GPRC5D), an orphan receptor of unknown physiological function, has been shown to be expressed on the cell surface of myeloma cells independently of BCMA and has been identified as an alternative immunotherapeutic target antigen for this indication2,3.

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Acknowledgements

K.N. and S.M. gratefully acknowledge the US National Cancer Institute Cancer Centre Support Grant (P30 CA008748) to Memorial Sloan Kettering Cancer Centre.

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Authors and Affiliations

  1. Department of Medicine, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Karthik Nath & Sham Mailankody

  2. Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Bruno A. Costa

  3. Department of Medicine, Myeloma Service, Memorial Sloan Kettering Cancer, New York, NY, USA

    Sham Mailankody

  4. Department of Medicine, Weill Cornell Medicine, New York, NY, USA

    Sham Mailankody

Authors
  1. Karthik Nath
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  2. Bruno A. Costa
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  3. Sham Mailankody
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Correspondence to Sham Mailankody.

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Competing interests

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 20, 281–282 (2023). https://doi.org/10.1038/s41571-023-00735-4

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