GPRC5D-Targeted CAR T Cells for Myeloma
Open accessAbstract
BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have generated responses in patients with advanced myeloma, but relapses are common. G protein-coupled receptor, class C, group 5, member D (GPRC5D) has been identified as an immunotherapeutic target in multiple myeloma. Preclinical studies have shown the efficacy of GPRC5D-targeted CAR T cells, including activity in a BCMA antigen escape model. METHODS: In this phase 1 dose-escalation study, we administered a GPRC5D-targeted CAR T-cell therapy (MCARH109) at four dose levels to patients with heavily pretreated multiple myeloma, including patients with relapse after BCMA CAR T-cell therapy. RESULTS: cells. CONCLUSIONS: 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. (Funded by Juno Therapeutics/Bristol Myers Squibb; ClinicalTrials.gov number, NCT04555551.).
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These results confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma.
“The most common grade 3 or higher adverse events (AEs) included neutropenia (94%), thrombocytopenia (65%), and anemia (35%), which confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma [229, 254].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [229]
The Results section (Safety and Maximum Tolerated Dose) reports the cited rates of grade 3 or higher neutropenia, thrombocytopenia, and anemia. The Abstract Conclusions explicitly say the study confirms GPRC5D as an active immunotherapeutic target, but the paper attributes those hematologic adverse events primarily to lymphodepleting chemotherapy; it does not present the adverse events as what confirms the target’s activity. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCAR-T cells targeting GPRC5D, CD19, CD38, CD138, CS1, and NKG2D are under exploration for MM treatment.
“Several CAR-T cells targeting antigens, such an GPRC5D [229–231], CD19 [232, 233], CD38 [234–236], CD138 [237], CS1 [238–240] and NKG2D [241, 242] are also under exploration for their efficacy in MM treatment.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [229]
The most common grade 3 or higher adverse events with MCARH109 included neutropenia (94%), thrombocytopenia (65%), and anemia (35%).
“The most common grade 3 or higher adverse events (AEs) included neutropenia (94%), thrombocytopenia (65%), and anemia (35%), which confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma [229, 254].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [229]
In the phase 1 trial of MCARH109, a response was reported in 71% (12/17) of the entire cohort of RRMM patients.
“Among the patients who received MCARH109 therapy, a response was reported in 71% (12/17) of the entire cohort.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [229]
35% (6/17) achieved a CR, while 59% (10/17) achieved VGPR or better.
“Of the total patients, 35% (6/17) achieved a CR, while 59% (10/17) achieved VGPR or better.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [229]
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- Authors
- Mailankody, S., Devlin, S. M., Landa, J., Nath, K., Diamonte, C., Carstens, E. J., Russo, D., Auclair, R., Fitzgerald, L., Cadzin, B., Wang, X., Sikder, D., Senechal, B., Bermudez, V. P., Purdon, T. J., Hosszu, K., McAvoy, D. P., Farzana, T., Mead, E., Wilcox, J. A., Santomasso, B. D., Shah, G. L., Shah, U. A., Korde, N., Lesokhin, A., Tan, C. R., Hultcrantz, M., Hassoun, H., Roshal, M., Sen, F., Dogan, A., Landgren, O., Giralt, S. A., Park, J. H., Usmani, S. Z., Rivière, I., Brentjens, R. J., & Smith, E. L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- From the Myeloma Service (S.M., U.A.S., N.K., A.L., C.R.T., M.H., H.H., O.L., S.Z.U.), the Cellular Therapy Service (S.M., K.N., L.F., B.C., T.F., G.L.S., A.L., S.A.G., J.H.P., S.Z.U.), the Adult Bone Marrow Transplantation Service (G.L.S., S.A.G.), and the Leukemia Service (J.H.P.), Department of Medicine, the Departments of Epidemiology and Biostatistics (S.M.D.), Radiology (J.L.), and Pathology and Laboratory Medicine (R.A., M.R., F.S., A.D.), the Cell Therapy and Cell Engineering Facility (X.W., D.S., B.S., V.P.B., I.R.), the Center for Cell Engineering and the Molecular Pharmacology Program (X.W., I.R.), and the Departments of Pediatrics (K.H., D.P.M.), Anesthesiology and Critical Care Medicine (E.M., S.Z.U.), and Neurology (J.A.W., B.D.S.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College (S.M., G.L.S., U.A.S., N.K., A.L., C.R.T., M.H., H.H., S.A.G., J.H.P., S.Z.U.), New York, and the Department of Medicine, Roswell Park Comprehensive Cancer Center...
- ORCID
- Mailankody, Sham
- Devlin, Sean M.
- Landa, Jonathan
- Nath, Karthik
- Carstens, Elizabeth J.
- Auclair, Romany
- Purdon, Terence J.
- Hosszu, Kinga
- McAvoy, Devin P.
- Wilcox, Jessica A.
- Santomasso, Bianca D.
- Shah, Gunjan L.
- Shah, Urvi A.
- Korde, Neha
- Lesokhin, Alexander
- Tan, Carlyn R.
- Hultcrantz, Malin
- Hassoun, Hani
- Roshal, Mikhail
- Landgren, Ola
- Giralt, Sergio A.
- Park, Jae H.
- Usmani, Saad Z.
- Rivière, Isabelle
- Brentjens, Renier J.
- Smith, Eric L.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-09-29
- Volume
- 387
- Issue
- 13
- Pages
- 1196-1206
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC10309537
- OpenAlex
- W4297519419
- Cited by
- 411
- References
- 7
- Citations by year
- 2026: 58 · 2025: 106 · 2024: 137 · 2023: 101 · 2022: 7 · 2013: 1
- FWCI
- 36.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- National Cancer Institute (P30 CA008748)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- GPRC5D, multiple myeloma, CAR T-cell therapy, BCMA, relapsed multiple myeloma, dose escalation, immunotherapy targets
- MeSH terms
- Receptors, Chimeric Antigen, Cytokine Release Syndrome, Humans, Multiple Myeloma, Neoplasm Recurrence, Local, T-Lymphocytes, Immunotherapy, Adoptive, Receptors, G-Protein-Coupled, B-Cell Maturation Antigen
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