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ASH 2020 | Biallelic BCMA loss causes anti-BCMA CAR-T resistance in myeloma

Mehmet Samur, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses an investigation into the mechanisms of resistance to the B-cell maturation antigen-directed (BCMA) chimeric antigen receptor (CAR)-T cell therapy, idecabtagene vicleucel (ide-cel), which may be the underlying cause of relapse in multiple myeloma patients receiving this treatment. A myeloma patient who initially achieved a partial response showed no response to high-dose retreatment at relapse. Tumor intrinsic factors were explored and it was found that soluble BCMA levels fell drastically following the first infusion and remained low following relapse. Mutational analysis revealed that the BCMA locus on the 16p chromosome was deleted and a nonsense mutation in BCMA was identified, resulting in biallelic BCMA deletion. This case study highlights biallelic loss as a potential CAR-T resistance mechanism. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.