Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma

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. In two cases, MM relapse post-TCE/CAR T therapy was driven by…

• MM
  Multiple Myeloma Research Foundation
• A
  Amgen
• P
  Pfizer
• C
  Celgene
• CC
  Comprehensive Cancer Center, City of Hope
• UO
  University of Calgary
• HR
  Health Research Board
• SC
  Sylvester Comprehensive Cancer Center, University of Miami Health Systems

  Award: P30 CA 240139
• GP
  Glenmark Pharmaceuticals
• TF
  Terry Fox Foundation
• DK
  Deutsche Krebshilfe
• RT
  Rising Tide Foundation
• G
  Genentech
• NC
  National Cancer Institute

  Award: P30 CA 240139