A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Michael Rade - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • David Fandrei - , Fraunhofer Institute for Cell Therapy and Immunology, Leipzig University (Author)
  • Markus Kreuz - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Sabine Seiffert - , Leipzig University (Author)
  • Anja Grahnert - , Leipzig University (Author)
  • Maik Friedrich - , Leipzig University (Author)
  • Thomas Wiemers - , Leipzig University (Author)
  • Patrick Born - , Leipzig University (Author)
  • Luise Fischer - , Leipzig University (Author)
  • Heike Weidner - , Department of Internal Medicine III, University Centre for Healthy Ageing (Author)
  • Lorenz C. Hofbauer - , Department of Internal Medicine III, University Centre for Healthy Ageing (Author)
  • Ronny Baber - , Leipzig University (Author)
  • Song Yau Wang - , Leipzig University (Author)
  • Enrica Bach - , Leipzig University (Author)
  • Sandra Hoffmann - , Leipzig University (Author)
  • Jonathan Scolnick - , Singleron Biotechnologies (Author)
  • Mirco Friedrich - , Broad Institute of Harvard University and MIT (Author)
  • Farid Keramati - , Princess Máxima Center for Pediatric Oncology (Author)
  • Peter Brazda - , Princess Máxima Center for Pediatric Oncology, Utrecht University (Author)
  • Zsolt Sebestyen - , Utrecht University (Author)
  • Jürgen Kuball - , Utrecht University (Author)
  • Miriam Alb - , Fraunhofer Institute for Cell Therapy and Immunology, University of Würzburg (Author)
  • Lukas Scheller - , University of Würzburg (Author)
  • Michael Hudecek - , Fraunhofer Institute for Cell Therapy and Immunology, University of Würzburg (Author)
  • Hermann Einsele - , University of Würzburg (Author)
  • Klaus H. Metzeler - , Leipzig University (Author)
  • Marco Herling - , Leipzig University (Author)
  • Carmen Diana Herling - , Leipzig University (Author)
  • Madlen Jentzsch - , Leipzig University (Author)
  • Georg Nikolaus Franke - , Leipzig University (Author)
  • Andreas Boldt - , Leipzig University (Author)
  • Ulrike Köhl - , Fraunhofer Institute for Cell Therapy and Immunology, Leipzig University (Author)
  • Uwe Platzbecker - , Department of Internal Medicine I, University Hospital Leipzig, University Hospital Carl Gustav Carus Dresden, Central German Cancer Center - Partner Site Leipzig (Author)
  • Vladan Vucinic - , Leipzig University (Author)
  • Kristin Reiche - , Fraunhofer Institute for Cell Therapy and Immunology, Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI) Dresden/Leipzig, University Hospital Leipzig, Central German Cancer Center - Partner Site Leipzig (Author)
  • Maximilian Merz - , Fraunhofer Institute for Cell Therapy and Immunology, Leipzig University, Memorial Sloan-Kettering Cancer Center (Author)

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 languageEnglish
Pages (from-to)586-603.e9
Number of pages27
JournalCancer cell
Volume44
Issue number3
Early online date4 Dec 2025
Publication statusPublished - 9 Mar 2026
Peer-reviewedYes

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