Single-Cell Analysis of the Multiple Myeloma Microenvironment after Gamma-Secretase Inhibition and CAR T-Cell Therapy

We examined the effects of gamma-secretase inhibition (GSI) on the bone marrow microenvironment in multiple myeloma patients before anti-B-cell maturation antigen (BCMA) CAR T-cell therapy. Single-nuclei RNA and ATAC sequencing revealed significant changes in gene expression and chromatin accessibility, especially in monocytes and tumor cells, following exposure to GSI. The findings suggest that GSI influences not only BCMA signaling but also broader cellular interactions within the tumor microenvironment. De-identified sequencing data from the study is available through dbGaP.]]>
Bone marrow aspirates were obtained from 16 participants enrolled in a phase I clinical trial investigating GSI (crenigacestat) in combination with anti-BCMA CAR T-cells (FCARH143) (Lancet Oncol. 2023;24(7):811–822). Samples were collected at screening and following GSI administered orally every 48 hours for three doses.]]>