Overview of study design. (A) GSI increase antigen density on MM cells by inhibiting γ-secretase–mediated cleavage of BCMA, thereby improving recognition of anti-BCMA CAR T-cell therapy for MM. (B) Timeline of a prior phase 1 clinical trial that assessed the safety of GSI for patients with MM receiving anti-BCMA CAR T-cell therapy, serving as the source for our study samples. (C) The design of this study was to interrogate the bone marrow microenvironment using single-cell multiome ATAC plus gene expression of 16 clinical trial patients before and after exposure to 3 doses of oral GSI (crenigacestat). QOD, every other day.