BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells

Müller F, Wirsching A, Hagen M, Völkl S, Tur C, Raimondo MG, Taubmann J, Bucci L, Zhang L, Kretschmann S, Aigner M, Eckstein M, Spörl S, Kharboutli S, Böltz S, Atzinger A, Munoz LE, Schett G, Mackensen A, Grieshaber Bouyer R (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Nature Medicine Nature Publishing Group

Book Volume: 31

Pages Range: 1793-1797

DOI: 10.1038/s41591-025-03718-3

Abstract

CD19 chimeric antigen receptor (CD19 CAR) T cell therapy has been shown to induce stable drug-free remission in patients with refractory autoimmune disease. The management of potential relapses is currently unclear. Here we report on a 45-year-old woman with treatment-refractory Jo-1-associated anti-synthetase syndrome, who initially achieved disease remission after CD19 CAR T cell therapy but then experienced disease relapse after 9 months. After reinfusion of the same product, CAR T cells failed to expand and T cells targeting the CD19 CAR were detected. Despite full-dose lymphodepletion, no clinical response was observed. After bridging with anti-CD38 antibody daratumumab, which was efficacious with limited durability, plasma-cell-targeting B-cell maturation antigen (BCMA) CAR T cell therapy was performed. BCMA CAR T cells expanded, cleared plasma cells in lymphoid tissue, reduced autoantibody levels and re-induced stable drug-free remission. This case highlights the challenges in CAR T cell reinfusion, the potential of alternative targets and products, and suggests that the depletion of plasma cells may enhance therapeutic outcomes in patients who become treatment-refractory.

Authors with CRIS profile

Fabian Müller Department of Medicine 5 – Haematology and Oncology Melanie Hagen Department of Medicine 3 – Rheumatology and Immunology Simon Völkl Department of Medicine 5 – Haematology and Oncology Carlo Tur Department of Medicine 3 – Rheumatology and Immunology Maria Gabriella Raimondo Department of Medicine 3 – Rheumatology and Immunology Jule Taubmann Department of Medicine 3 – Rheumatology and Immunology Laura Bucci Department of Medicine 3 – Rheumatology and Immunology Liang Zhang Department of Medicine 3 – Rheumatology and Immunology Sascha Kretschmann Department of Medicine 5 – Haematology and Oncology Markus Eckstein Institute of Pathology Silvia Spörl Department of Medicine 5 – Haematology and Oncology Sebastian Böltz Department of Medicine 3 – Rheumatology and Immunology Armin Atzinger Department of Nuclear Medicine Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Andreas Mackensen Lehrstuhl für Innere Medizin V Ricardo Grieshaber Bouyer Professur für Klinische Systemimmunologie

How to cite

APA:

Müller, F., Wirsching, A., Hagen, M., Völkl, S., Tur, C., Raimondo, M.G.,... Grieshaber Bouyer, R. (2025). BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells. Nature Medicine, 31, 1793-1797. https://doi.org/10.1038/s41591-025-03718-3

MLA:

Müller, Fabian, et al. "BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells." Nature Medicine 31 (2025): 1793-1797.

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