Decentralised, point-of-care CAR-T for multiple myeloma

BCMA chimeric antigen receptor (CAR) T-cell therapy represents a major breakthrough in the treatment of multiple myeloma. 1 Roex G Timmers M Wouters K et al. Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. J Hematol Oncol. 2020; 13: 164 Crossref PubMed Scopus (58) Google Scholar Idecabtagene vicleucel and ciltacabtagene autoleucel are so far the only two industrial BCMA CAR T-cell therapies that have received regulatory approval. 2 Rodriguez-Otero P Ailawadhi S Arnulf B et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023; 388: 1002-1014 Crossref PubMed Scopus (10) Google Scholar , 3 Martin T Usmani SZ Berdeja JG et al. Ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2023; 41: 1265-1274 Crossref PubMed Scopus (63) Google Scholar Both have shown unprecedented clinical efficacy, translating into progression-free survival that largely exceeds the expected 3–4-month progression-free survival in relapsed or refractory multiple myeloma. 2 Rodriguez-Otero P Ailawadhi S Arnulf B et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023; 388: 1002-1014 Crossref PubMed Scopus (10) Google Scholar , 3 Martin T Usmani SZ Berdeja JG et al. Ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2023; 41: 1265-1274 Crossref PubMed Scopus (63) Google Scholar , 4 Delforge M Vekemans M-C Depaus J et al. Ciltacabtagene autoleucel for patients with triple-class exposed multiple myeloma: adjusted comparison of CARTITUDE-1 patient outcomes versus real-world clinical practice. HemaSphere. 2022; 6: e813 Crossref PubMed Scopus (0) Google Scholar In The Lancet Oncology, Aina Oliver-Caldés and colleagues 5 Oliver-Caldés A González-Calle V Cabañas V et al. Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. Lancet Oncol. 2023; (published online July 3.)https://doi.org/10.1016/S1470-2045(23)00222-X Google Scholar report the results of ARI0002h, a BCMA CAR T-cell therapy developed in Spain by an academic group, in 30 patients with relapsed or refractory multiple myeloma. Similar to an Israeli initiative, 6 Asherie N Kfir-Erenfeld S Avni B et al. Development and manufacturing of novel locally produced anti-BCMA CART cells for the treatment of relapsed/refractory multiple myeloma: phase I clinical results. Haematologica. 2022; (published online Oct 6.)https://doi.org/10.3324/haematol.2022.281628 Crossref PubMed Google Scholar this study confirms that in-house production of CAR T cells in an academic setting and according to good manufacturing practice standards is feasible, resulting in high-quality products with potent activity. All 30 patients responded, and a complete response or better was observed in 20 (67%) patients after a median follow-up of 18 months (IQR 15–20). The median progression-free survival was 14·5 months (95% CI 12·8–not reached). Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot studyARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach. Full-Text PDF