Expert Shares Rationale for GSI Plus CAR T-Cell Combination in Myeloma

Feb 13, 2020

Andrew J. Cowan, MD, explains the rationale for a phase I clinical trial in which a gamma-secretase inhibitor was combined with CAR T-cell therapy as treatment for heavily pretreated patients with multiple myeloma.

Andrew J. Cowan, MD, assistant professor of Medicine, Division of Medical Oncology, University of Washington School of Medicine; physician at Seattle Cancer Care Alliance; and assistant member in the Clinical Research Division, Fred Hutchinson Cancer Research Center, explains the rationale for a phase I clinical trial in which a gamma-secretase inhibitor (GSI) was combined with CAR T-cell therapy as treatment for heavily pretreated patients with multiple myeloma.

BCMA is a commonly used target for CAR T cells in multiple myeloma. Preclinical research shows that gamma-secretase, a cell membrane protein which is involved with cleavage of BCMA from the surface of plasma cells. Other preclinical research has shown that using GSIs can block the action of gamma-secretase, increase BCMA expression on the surface of plasma cells and reduce soluble BCMA.

Based on these preclinical studies, Cowan et al hypothesized that by combining GSIs with BCMA CAR T-cell therapy, the anti-tumor efficacy of the GSIs would be increased.

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