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.

Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma / M.C. Da Vià, O. Dietrich, M. Truger, P. Arampatzi, J. Duell, A. Heidemeier, X. Zhou, S. Danhof, S. Kraus, M. Chatterjee, M. Meggendorfer, S. Twardziok, M.-. Goebeler, M.S. Topp, M. Hudecek, S. Prommersberger, K. Hege, S. Kaiser, V. Fuhr, N. Weinhold, A. Rosenwald, F. Erhard, C. Haferlach, H. Einsele, K.M. Kortum, A.-. Saliba, L. Rasche. - In: NATURE MEDICINE. - ISSN 1078-8956. - 27:4(2021), pp. 616-619. [10.1038/s41591-021-01245-5]

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

M.C. Da Vià
Primo
;
2021

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.
Aged; Antigens, Neoplasm; B-Cell Maturation Antigen; DNA Copy Number Variations; Homozygote; Humans; Magnetic Resonance Imaging; Male; Multiple Myeloma; Receptors, Chimeric Antigen; T-Lymphocytes; Gene Deletion
Settore MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/892430
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