Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma
Leipold AM, Werner RA, Duell J, Jung P, John M, Stanojkovska E, Zhou X, Hornburger H, Ruckdeschel A, Dietrich O, Imdahl F, Krammer T, Knop S, Rosenwald A, Buck A, Sander LE, Einsele H, Kortuem KM, Saliba AE, Rasche L (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 37
Pages Range: 650-658
Journal Issue: 3
DOI: 10.1038/s41375-023-01824-0
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.
Involved external institutions
Helmholtz-Zentrum für Infektionsforschung (HZI)
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Freie Universität Berlin
Germany (DE)
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Freie Universität Berlin
Germany (DE)
How to cite
APA:
Leipold, A.M., Werner, R.A., Duell, J., Jung, P., John, M., Stanojkovska, E.,... Rasche, L. (2023). Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma. Leukemia, 37(3), 650-658. https://doi.org/10.1038/s41375-023-01824-0
MLA:
Leipold, Alexander M., et al. "Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma." Leukemia 37.3 (2023): 650-658.
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