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Peer-Reviewed Publication
Transplant Cell Ther2025;31(12):1002.e1-1002.e9.December 1, 2025Journal Article

Impact of Gamma-Secretase Inhibition on Outcomes Following BCMA CAR-T Therapy in Multiple Myeloma: A Comparison of Two Phase 1 Trials.

Andrew J Portuguese1, Sherilyn A Tuazon2, Margot J Pont3, Gabriel O Cole3, Blythe D Sather4, Xiaoling Song5, Sushma Thomas5, Brent L Wood6, Michelle Blake7, Melissa G Works8, Mazyar Shadman1, Emily C Liang1, Vicky Q Wu1, Jenna M Voutsinas1, Ted A Gooley5, Cameron J Turtle9, Brian G Till1, David G Coffey10, David G Maloney1, Edward N Libby1, Aude G Chapuis1, Filippo Milano1, Stanley R Riddell1, Damian J Green11, Andrew J Cowan1
1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Division of Hematology and Oncology, University of Washington, Seattle, Washington.
2Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Division of Hematology and Oncology, University of Washington, Seattle, Washington; Cell Therapy, Juno Therapeutics, a Bristol Myers Squibb Company, Seattle, Washington.
3Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Translational Sciences, Galapagos NV, Mechelen, Belgium.
4Cell Therapy, Juno Therapeutics, a Bristol Myers Squibb Company, Seattle, Washington; Research, Tune Therapeutics, Seattle, Washington.
5Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.
6Division of Hematology and Oncology, University of Washington, Seattle, Washington; Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California.
7Cell Therapy, Juno Therapeutics, a Bristol Myers Squibb Company, Seattle, Washington; Translational Sciences, Sonoma Biotherapeutics, Seattle, Washington.
8Cell Therapy, Juno Therapeutics, a Bristol Myers Squibb Company, Seattle, Washington; Therapeutic Pipeline, AltPep, Seattle, Washington.
9Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Cancer Immunotherapy, The University of Sydney, Camperdown, New South Wales, Australia; Haematology and Transfusion Medicine, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
10Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Division of Hematology and Oncology, University of Washington, Seattle, Washington; Translational Research, Sylvester Comprehensive Cancer Center, Miami, Florida; Division of Transplantation and Cellular Therapy, University of Miami, Miami, Florida.
11Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Division of Hematology and Oncology, University of Washington, Seattle, Washington; Translational Research, Sylvester Comprehensive Cancer Center, Miami, Florida; Division of Transplantation and Cellular Therapy, University of Miami, Miami, Florida. Electronic address: damiangreen@miami.edu.
PubMed DOI

Abstract

BACKGROUND: BCMA-directed chimeric antigen receptor (CAR)-T cell therapy represents a major therapeutic breakthrough for relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses in heavily pretreated patients. However, a subset of patients experiences early relapse or fail to respond, highlighting the need for strategies to enhance efficacy. Gamma-secretase inhibitors (GSIs…

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