Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma
Alexander M. Leipold, Rudolf A. Werner, Johannes Düll, Pius Jung, Mara John, Emilia Stanojkovska, Xiang Zhou, Hannah Hornburger, Anna Ruckdeschel, Oliver Dietrich, Fabian Imdahl, Tobias Krammer, Stefan Knop, Andreas Rosenwald, Andreas K. Buck, Leif Erik Sander, Hermann Einsele, K. Martin Kortüm, Antoine‐Emmanuel Saliba, Leo Rasche
Abstract
Pseudo-progression and flare-up phenomena constitute a novel diagnostic challenge in the follow-up of patients treated with immune-oncology drugs. We present a case study on pulmonary flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T-cell therapy, and used single-cell RNA-seq (scRNA-seq) to identify a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon. By integrating datasets of various lung pathological conditions, we revealed transcriptomic similarities between post CAR T pulmonary lesions and sarcoidosis. Furthermore, we explored a noninvasive PET based diagnostic approach and showed that tracers binding to CXCR4 complement FDG PET imaging in this setting, allowing discrimination between immune-mediated changes and true relapse after CAR T-cell treatment. In conclusion, our study highlights a Th17.1 driven autoimmune phenomenon after CAR T, which may be misinterpreted as disease relapse, and that imaging with multiple PET tracers and scRNA-seq could help in this diagnostic dilemma.