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 maximum tolerated dose of 150 × 10<sup>6</sup> 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.
Authors
- Heather Jolie Landau (ORCID: https://orcid.org/0000-0002-3152-1189)
- Saad Z. Usmani (ORCID: https://orcid.org/0000-0002-5484-8731)
- Kinga Hosszu (ORCID: https://orcid.org/0000-0002-1190-1491)
- Malin L. Hultcrantz (ORCID: https://orcid.org/0000-0002-9045-6495)
- Gunjan L. Shah (ORCID: https://orcid.org/0000-0002-9977-0456)
- Urvi Ashok Shah (ORCID: https://orcid.org/0000-0001-8419-1091)
- Özgür Can Eren (ORCID: https://orcid.org/0000-0001-9889-2702)
- Ahmet Doǧan (ORCID: https://orcid.org/0000-0001-6576-5256)
- Jonathan Landa (ORCID: https://orcid.org/0000-0002-5437-4951)
- Alexander M. Lesokhin (ORCID: https://orcid.org/0000-0001-9321-702X)
- Isabelle Rivière
- Hani Hassoun
- Sean M. Devlin (ORCID: https://orcid.org/0000-0002-6801-720X)
- Michael Scordo (ORCID: https://orcid.org/0000-0002-9484-0240)
- Devin McAvoy (ORCID: https://orcid.org/0000-0001-7807-6775)
- Eric Matthew Jurgens (ORCID: https://orcid.org/0000-0001-8280-2581)
- David J. Chung (ORCID: https://orcid.org/0000-0003-0469-839X)
- Sham Mailankody (ORCID: https://orcid.org/0000-0002-2815-9561)
- Neha Korde (ORCID: https://orcid.org/0000-0002-5538-4318)
- Renier J. Brentjens (ORCID: https://orcid.org/0000-0002-3364-5388)
- Sergio A. Giralt (ORCID: https://orcid.org/0000-0003-1944-5053)
- Carlyn Rose C. Tan (ORCID: https://orcid.org/0000-0001-7922-2594)
- Ross Firestone (ORCID: https://orcid.org/0000-0002-2945-9320)
- Eric L. Smith (ORCID: https://orcid.org/0000-0002-0296-7587)
- Xiuyan Wang
- Jae H. Park (ORCID: https://orcid.org/0000-0002-2903-5130)
- Jagrutiben Chaudhari
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Dana-Farber Cancer Institute (US)
Publication Details
- Journal
- Journal of Clinical Oncology
- Published
- 2024-12-04
- DOI
- https://doi.org/10.1200/jco-24-01785
- Citations
- 19
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 5.37