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

Matteo C. Da Vià, Oliver Dietrich, Marietta Truger, Panagiota Arampatzi, Johannes Duell, Anke Heidemeier, Xiang Zhou, Sophia Danhof, Sabrina Kraus, Manik Chatterjee, Manja Meggendorfer, Sven Twardziok, Maria-Elisabeth Goebeler, Max S. Topp, Michael Hudecek, Sabrina Prommersberger, Kristen Hege, Shari Kaiser, Viktoria Fuhr, Niels Weinhold, Andreas Rosenwald, Florian Erhard, Claudia Haferlach, Hermann Einsele, K. Martin Kortüm, Antoine-Emmanuel Saliba and Leo Rasche

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.

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Species: human
Number of cells: 5669
Number of downloads: 48
Study size: 323MB
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Multiple myeloma 
Bone marrow 
CAR-T cell