Ruxolitinib for ciltacabtagene autoleucel–associated refractory diarrhea
Abstract
Abstract Intractable diarrhea is a recently described complication following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma with reported mortality rates of 36% to 50%. The optimal clinical management is unknown. Here, we report a series of 5 patients who presented with severe diarrhea after BCMA CAR T-cell treatment. We hypothesized that the Janus kinase inhibitor, ruxolitinib, might be an effective therapy based on its success in graft-versus-host-disease after allogeneic bone marrow transplant and other immune-driven diarrhea syndromes. Three patients received ruxolitinib, all of whom experienced rapid clinical improvement. Among the 2 patients with matched pretreatment and posttreatment biopsies, both showed signs of histopathologic response, including 1 with CAR T-cell–associated indolent T-cell lymphoproliferative disease of the gastrointestinal tract.
Article Details
Authors (41)
Viktoria Blumenberg
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Filippo Birocchi
Angela Shih
Giulia Escobar
Adele Mucci
Alexander Armstrong
Diana Cirstea
3Hematology and Oncology Division, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Deshea L. Harris
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
David J. Bozym
3Hematology and Oncology Division, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Benjamin R. Puliafito
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Richard Newcomb
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Tejaswini M. Dhawale
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Patrick C. Johnson
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Areej El-Jawahri
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Richard Jeffrey
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Alexis L. Barselau
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Alex Li
Estelle Emmanuel-Alejandro
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Daniella Cook
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Kevin Lindell
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Samantha O. Luk
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Ryan Chaffee
Andrew J. Yee
Department of Medicine, Harvard Medical School, Boston
Andrew Branagan
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Noopur Raje
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Charlotte E. Graham
4Comprehensive Cancer Centre, King’s College London, London, United Kingdom
Sarah P. Hammond
3Hematology and Oncology Division, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Frederic D. Bushman
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Aoife M. Roche
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Shantan Reddy
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Alexander G. McFarland
6Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Yi-Bin Chen
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Bryan D. Choi
Christopher W. Mount
2Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Michael Dougan
8Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Valentina Nardi
Mayo Clinic, Rochester, Minnesota, United States
Aliyah R. Sohani
2Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Kathleen M. E. Gallagher
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Marcela V. Maus
Matthew J. Frigault
3Massachusetts General Hospital, Boston, MA
Mark B. Leick