Holly Lee, Sungwoo Ahn, Ranjan Maity, Noemie Leblay, Bachisio Ziccheddu, Marietta Truger, Monika Chojnacka, Anthony Cirrincione, Michael Durante, Remi Tilmont, Elie Barakat, Mansour Poorebrahim, Sarthak Sinha, John McIntyre, Angela M Y Chan, Holly Wilson, Shari Kyman, Amrita Krishnan, Ola Landgren, Wencke Walter, Manja Meggendorfer, Claudia Haferlach, Torsten Haferlach, Hermann Einsele, Martin K Kortüm, Stefan Knop, Jean Baptiste Alberge, Andreas Rosenwald, Jonathan J Keats, Leo Rasche, Francesco Maura, Paola Neri, Nizar J Bahlis
B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy...
August 31, 2023: Nature Medicine