Ruxolitinib for ciltacabtagene autoleucel-associated refractory diarrhea

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.