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Viktoria Blumenberg¹, Filippo Birocchi¹, Angela Shih²

¹Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.

|January 27, 2026

Summary

Severe diarrhea after chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM) can be fatal. Ruxolitinib, a Janus kinase (JAK) inhibitor, shows promise in treating this complication, leading to rapid clinical improvement in patients.

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Area of Science:

Oncology
Immunotherapy
Gastroenterology

Background:

Intractable diarrhea is a severe complication of B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM).
This complication has high mortality rates (36-50%), and optimal management strategies are lacking.
Immune-driven diarrhea syndromes and graft-versus-host-disease (GVHD) after allogeneic bone marrow transplant have shown response to Janus kinase (JAK) inhibitors.

Purpose of the Study:

To investigate the efficacy of ruxolitinib for managing intractable diarrhea following BCMA-targeted CAR T-cell therapy.
To evaluate clinical and histopathological responses to ruxolitinib treatment in affected patients.

Main Methods:

Retrospective case series of five patients with severe diarrhea post-BCMA CAR T-cell therapy.
Treatment with ruxolitinib was administered to three patients.
Pre- and post-treatment biopsies were analyzed in two patients.

Main Results:

Three patients treated with ruxolitinib experienced rapid clinical improvement.
Histopathological analysis of biopsies revealed a positive response in both patients with matched samples.
One patient showed signs of CAR T cell-associated indolent T-cell lymphoproliferative disease of the gastrointestinal tract (ITLPD-GT).

Conclusions:

Ruxolitinib may be an effective therapeutic option for intractable diarrhea following BCMA-targeted CAR T-cell therapy.
Further research is warranted to confirm these findings and establish treatment guidelines.
Early intervention with ruxolitinib could potentially improve outcomes and reduce mortality in this patient population.