A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma
Research output: Contribution to journal › Research article › Contributed › peer-review
Abstract
Chimeric antigen receptor (CAR) T cell therapies targeting B cell maturation antigen (BCMA) are transforming treatment for relapsed or refractory multiple myeloma (RRMM). We analyze 61 RRMM patients receiving idecabtagene vicleucel (Ide-cel; n = 34) or ciltacabtagene autoleucel (Cilta-cel; n = 27) and find that Cilta-cel achieves higher complete response (CR) rates (78% vs. 38%) and longer progression-free survival. Using a longitudinal single-cell multi-omics atlas of 135 blood samples, we show that Cilta-cel induces expansion of CD4+ cytotoxic T cells associated with CR and immune-related toxicities, whereas non-CR CD8+ T cells display impaired effector programs. Among non-B cells, plasmacytoid dendritic cells (pDCs) show the highest BCMA expression and BCMA-targeted agents eradicate a blastic plasmacytoid dendritic cell neoplasm line, suggesting a novel therapeutic avenue for this disease. Greater reductions in soluble BCMA correlate with enhanced CAR T expansion and systemic inflammation. These findings reveal cellular mechanisms driving differential efficacy and toxicity of BCMA-directed immunotherapy.
Details
| Original language | English |
|---|---|
| Pages (from-to) | 586-603.e9 |
| Number of pages | 27 |
| Journal | Cancer cell |
| Volume | 44 |
| Issue number | 3 |
| Early online date | 4 Dec 2025 |
| Publication status | Published - 9 Mar 2026 |
| Peer-reviewed | Yes |
External IDs
| PubMed | 41349540 |
|---|---|
| ORCID | /0000-0002-8691-8423/work/202353968 |
| ORCID | /0009-0001-6045-3349/work/202354146 |
Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- B cell maturation antigen, blastic plasmacytoid dendritic cell neoplasm, chimeric antigen receptor T cells, multiple myeloma, single-cell sequencing, T cell receptor