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Research Offers Insights on Resistance Mechanisms of BCMA CAR T-Cell Therapy for Myeloma

By: Celeste L. Dixon
Posted: Monday, August 28, 2023

The immune microenvironment of bone marrow may be responsible for the short remission time and high relapse rate of patients with multiple myeloma who are treated with B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy. Thus, Yongping Song, MD, PhD, of the First Affiliated Hospital of Zhengzhou University, Henan, China, and colleagues undertook single-cell RNA sequencing of bone marrow plasma cells and immune cells to analyze resistance mechanisms and to explore potential novel therapeutic targets for relapsed multiple myeloma after this type of immunotherapy. Among their findings was that at relapse, the proportion of monocytes/macrophages and the percentage of BCMA-positive plasma cells were both increased, and the percentage of T cells was decreased, the team reported in Experimental Hematology & Oncology.

Additionally, “cell-cell communication analysis indicated that monocytes/macrophages, especially in the MIF and APRIL signaling pathways, are key players in [patients with relapsed or refractory multiple myeloma] at relapse after BCMA CAR-T cell therapy,” the authors wrote. They used single-cell RNA sequencing to identify cell populations and the populations’ heterogeneity in relapsed or refractory multiple myeloma CD45-positive bone marrow cells before BCMA CAR T-cell therapy and in relapse after treatment.

Based on their data, the researchers suggested that “combination therapy aiming at additional multiple myeloma targets (such as CD38, CD24, CD138, SLAMF7, and GPRC5D) may be a better CAR-T treatment strategy to overcome the heterogeneity of multiple myeloma and avoid clonal selection based on the loss of one specific antigen.” Such approaches may include “bispecific CAR-T products, trispecific antibody CAR-T products, and CAR-T products in combination with single-target immunotherapies.”

Disclosure: The study authors reported no conflicts of interest.

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