A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma
Michael Rade, David Fandrei, Markus Kreuz, Sabine Seiffert, Anja Grahnert, Maik Friedrich, Thomas Wiemers, Patrick Born, Luise Fischer, Heike Weidner, Lorenz C. Hofbauer, Ronny Baber, Song‐Yau Wang, Enrica Bach, Sandra Hoffmann, Jonathan Scolnick, Mirco Friedrich, Farid Keramati, Péter Brázda, Zsolt Sebestyén, Jürgen Kuball, Miriam Alb, Lukas Scheller, Michael Hudecek, Hermann Einsele, Klaus H. Metzeler, Marco Herling, Carmen Herling, Madlen Jentzsch, Georg‐Nikolaus Franke, Andreas Boldt, Ulrike Koehl, Uwe Platzbecker, Vladan Vučinić, Kristin Reiche, Maximilian Merz
Abstract
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.