Phase 1 clinical trial of B-cell maturation antigen (BCMA) NEX-T® chimeric antigen receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma Journal Article
| Authors: | Ravi, G.; Richard, S.; Kumar, S.; Atrash, S.; Liedtke, M.; Kaur, G.; Derman, B.; Bergsagel, P. L.; Mailankody, S.; McCarthy, P.; Shrestha, A.; Kelly, L. M.; Ly, T.; Das, S.; Thorpe, J.; Maier, A.; Varun, D.; Navarro, G.; Burgess, M. R.; Hege, K.; Koegel, A. K.; Costa, L. J. |
| Article Title: | Phase 1 clinical trial of B-cell maturation antigen (BCMA) NEX-T® chimeric antigen receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma |
| Abstract: | BCMA-targeted CAR T-cells transformed the treatment of relapsed and refractory multiple myeloma (RRMM), yet improvements are needed in manufacturing, toxicity and efficacy. We conducted a phase 1 clinical trial of BMS-986354, an autologous BCMA CAR T manufactured using an optimized NEX-T® process, in participants with triple-class exposed, RRMM. The 65 participants had a median of 5 (range 3–13) prior regimens, 39% had cytogenetic high-risk, 91% triple-class refractory, and 43% extra-medullar disease. Part A (dose-escalation) of the study enrolled participants in cohorts receiving 20 (N = 7), 40 (N = 24), or 80 (N = 11)x 106 CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×106 CAR + T cells. Across dose levels, cytokine release syndrome (CRS) occurred in 82% (2% grade ≥3), neurotoxicity in 8% (2% grade ≥3), and infections in 32% of participants (5% grade ≥ 3). The response rate was 95%, with 46% achieving complete responses. Median progression-free survival was 12.3 months (95% CI 11.3–16). Compared to orvacabtagene autoleucel (same CAR construct, conventional manufacturing), BMS-986354 had higher proportion of T central memory cells, were less differentiated and had enhanced potency and proliferative capacity, supporting the use of NEX-T® in future CAR T development. © The Author(s) 2025. |
| Keywords: | adult; aged; middle aged; human cell; major clinical study; overall survival; fludarabine; lenalidomide; clinical trial; neutropenia; drug efficacy; drug safety; liver function; flow cytometry; neurotoxicity; follow up; cd8+ t lymphocyte; t lymphocyte; t-lymphocytes; phenotype; progression free survival; bortezomib; multiple myeloma; cell maturation; thrombocytopenia; morbidity; cohort analysis; cyclophosphamide; autologous stem cell transplantation; plasmacytoma; pathology; drug dose escalation; chromosome aberration; immunology; multicenter study; cd4+ t lymphocyte; chimeric antigen receptor; phase 1 clinical trial; corticosteroid; cytokine release; chemokine receptor ccr7; disease exacerbation; therapy; adoptive immunotherapy; immunotherapy, adoptive; pharmacokinetics; creatinine clearance; cd45ra antigen; platelet count; carfilzomib; copy number variation; adverse event; leukapheresis; apheresis; cytokine release syndrome; procedures; overall response rate; pomalidomide; high throughput sequencing; humans; human; male; female; article; droplet digital polymerase chain reaction; absolute neutrophil count; b cell maturation antigen; daratumumab; isatuximab; pharmacodynamic parameters; b-cell maturation antigen; chimeric antigen receptor t-cell immunotherapy; anakinra; receptors, chimeric antigen; orvacabtagene autoleucel; tnfrsf17 protein, human; mm1.s cell line; triple class exposed multiple myeloma |
| Journal Title: | Leukemia |
| Volume: | 39 |
| Issue: | 4 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-05-01 |
| Start Page: | 816 |
| End Page: | 826 |
| Language: | English |
| DOI: | 10.1038/s41375-025-02518-5 |
| PUBMED: | 39910285 |
| PROVIDER: | scopus |
| PMCID: | PMC11976278 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
