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 (MM) with reported mortality rates of 36-50%. The optimal clinical management is unknown. Here, we report a series of five patients who presented with severe diarrhea after BCMA CAR T-cell treatment. We hypothesized that the Janus kinase (JAK) inhibitor, ruxolitinib, might be an effective therapy based on its success in graft-versus-host-disease (GVHD) after allogeneic bone marrow transplant and other immune-driven diarrhea syndromes. Three patients received ruxolitinib, all of whom experienced rapid clinical improvement. Among the two with matched pre- and post-treatment biopsies, both showed signs of histopathologic response, including one with CAR T cell-associated indolent T-cell lymphoproliferative disease of the gastrointestinal tract (ITLPD-GT).