Phase I Trial of MCARH109, a G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma: An Updated Analysis

MCARH109 is a first-in-class G protein-coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory multiple myeloma. This phase I clinical trial included 17 patients and determined that MCARH109 is safe at a maxi...

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Published in:	Journal of clinical oncology Vol. 43; no. 5; p. 498
Main Authors:	Jurgens, Eric M, Firestone, Ross S, Chaudhari, Jagrutiben, Hosszu, Kinga, Devlin, Sean M, Shah, Urvi A, Landa, Jonathan, McAvoy, Devin P, Lesokhin, Alexander M, Korde, Neha, Hassoun, Hani, Tan, Carlyn R, Hultcrantz, Malin, Shah, Gunjan L, Landau, Heather J, Chung, David J, Scordo, Michael, Eren, Ozgur Can, Dogan, Ahmet, Giralt, Sergio A, Park, Jae H, Rivière, Isabelle, Brentjens, Renier J, Smith, Eric L, Wang, Xiuyan, Usmani, Saad Z, Mailankody, Sham
Format:	Journal Article
Language:	English
Published:	United States 10.02.2025
Subjects:	Adult Aged Female Humans Immunotherapy, Adoptive - adverse effects Immunotherapy, Adoptive - methods Male Middle Aged Multiple Myeloma - immunology Multiple Myeloma - mortality Multiple Myeloma - therapy Receptors, Chimeric Antigen - immunology Receptors, G-Protein-Coupled - immunology
ISSN:	1527-7755, 1527-7755
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Summary:	MCARH109 is a first-in-class G protein-coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory multiple myeloma. This phase I clinical trial included 17 patients and determined that MCARH109 is safe at a maximum tolerated dose of 150 × 10 CAR T cells. In this updated analysis, no new serious adverse events were reported at a median follow-up of 37 months. Overall, 12 (71%) of 17 patients responded, including seven (70%) of 10 patients previously treated with B-cell maturation antigen-targeted therapy. The median duration of response was 8.6 months (95% CI, 5.7 to not reached [NR]) with two patients sustaining a stringent complete response at the time of last follow-up, 32 months and 41 months, respectively. The median overall survival (OS) was NR and the 3-year OS estimate was 59% (95% CI, 40 to 88). Possible GPRC5D loss via immunohistochemistry was observed in 6 (60%) of 10 patients at relapse. High-dimensional spectral cytometry-based immune profiling associated an activated T-cell phenotype at apheresis with a response to MCARH109.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1527-7755 1527-7755
DOI:	10.1200/JCO-24-01785