Da Vià Matteo C, Dietrich Oliver, Truger Marietta, Arampatzi Panagiota, Duell Johannes, Heidemeier Anke, Zhou Xiang, Danhof Sophia, Kraus Sabrina, Chatterjee Manik, Meggendorfer Manja, Twardziok Sven, Goebeler Maria-Elisabeth, Topp Max S, Hudecek Michael, Prommersberger Sabrina, Hege Kristen, Kaiser Shari, Fuhr Viktoria, Weinhold Niels, Rosenwald Andreas, Erhard Florian, Haferlach Claudia, Einsele Hermann, Kortüm K Martin, Saliba Antoine-Emmanuel, Rasche Leo
Department of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.
Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany.
Nat Med. 2021 Apr;27(4):616-619. doi: 10.1038/s41591-021-01245-5. Epub 2021 Feb 22.
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.
Clin Cancer Res. 2013-1-23
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