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 Journal Article
| Authors: | Jurgens, E. M.; Firestone, R. S.; Chaudhari, J.; Hosszu, K.; Devlin, S. M.; Shah, U. A.; Landa, J.; McAvoy, D. P.; Lesokhin, A. M.; Korde, N.; Hassoun, H.; Tan, C. R.; Hultcrantz, M.; Shah, G. L.; Landau, H. J.; Chung, D. J.; Scordo, M.; Eren, O. C.; Dogan, A.; Giralt, S. A.; Park, J. H.; Rivière, I.; Brentjens, R. J.; Smith, E. L.; Wang, X.; Usmani, S. Z.; Mailankody, S. |
| Article Title: | 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 |
| Abstract: | 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 × 106 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. © American Society of Clinical Oncology. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; treatment response; aged; middle aged; unclassified drug; overall survival; clinical trial; follow up; multiple myeloma; drug dose escalation; immunology; chimeric antigen receptor; open study; phase 1 clinical trial; receptors, g-protein-coupled; g protein coupled receptor; therapy; adoptive immunotherapy; immunotherapy, adoptive; molecularly targeted therapy; adverse event; apheresis; procedures; cytometry; humans; human; male; female; article; b cell maturation antigen; chimeric antigen receptor t-cell immunotherapy; receptors, chimeric antigen; cell therapy agent; gprc5d protein, human; mcarh 109 |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 5 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-02-10 |
| Start Page: | 498 |
| End Page: | 504 |
| Language: | English |
| DOI: | 10.1200/jco-24-01785 |
| PUBMED: | 39631041 |
| PROVIDER: | scopus |
| PMCID: | PMC11798713 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Sham Mailankody -- Source: Scopus |
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