Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma

Da Via MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, Zhou X, Danhof S, Kraus S, Chatterjee M, Meggendorfer M, Twardziok S, Goebeler ME, Topp MS, Hudecek M, Prommersberger S, Hege K, Kaiser S, Fuhr V, Weinhold N, Rosenwald A, Erhard F, Haferlach C, Einsele H, Kortuem KM, Saliba AE, Rasche L (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Medicine Nature Publishing Group

Book Volume: 27

Pages Range: 616-619

Journal Issue: 4

DOI: 10.1038/s41591-021-01245-5

Abstract

B cell maturation antigen (BCMA) is a target for various immunotherapies and a biomarker for tumor load in multiple myeloma (MM). We report a case of irreversible BCMA loss in a patient with MM who was enrolled in the KarMMa trial (NCT03361748) and progressed after anti-BCMA CAR T cell therapy. We identified selection of a clone with homozygous deletion of TNFRSF17 (BCMA) as the underlying mechanism of immune escape. Furthermore, we found heterozygous TNFRSF17 loss or monosomy 16 in 37 out of 168 patients with MM, including 28 out of 33 patients with hyperhaploid MM who had not been previously treated with BCMA-targeting therapies, suggesting that heterozygous TNFRSF17 deletion at baseline could theoretically be a risk factor for BCMA loss after immunotherapy.

Involved external institutions

Universitätsklinikum Würzburg DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) MLL Münchner Leukämielabor GmbH DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE) Bristol-Myers Squibb US United States (USA) (US) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Da Via, M.C., Dietrich, O., Truger, M., Arampatzi, P., Duell, J., Heidemeier, A.,... Rasche, L. (2021). Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nature Medicine, 27(4), 616-619. https://doi.org/10.1038/s41591-021-01245-5

MLA:

Da Via, Matteo C., et al. "Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma." Nature Medicine 27.4 (2021): 616-619.

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