Kenneth Lim, MBBS, Yi Lin, MD, Navreet Chowla, MD, FACG Mayo Clinic, Rochester, MN Introduction: Cilta-cel is a highly effective chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) app for refractory Multiple Myeloma patients. We examined the clinical course and outcomes of CAR-T related enterocolitis. Methods: Electronic medical records of multiple myeloma patients receiving CAR-T therapy and developing enterocolitis between 02/2022 and 12/2024 were reviewed. Results: There were 235 patients who underwent CAR-T therapy for Multiple Myeloma and nine (3.8%) developed ≥ Common Terminology Criteria for Adverse Effects (CTCAE) Grade 3 diarrhea. The median time for onset was 3.5 months (range 1.2-5.6). The median age was 65 years (range,31-86) and 53% were male. Patients had received a median of 4 prior lines of therapy prior to CAR-T therapy. The diarrhea was severe and required hospitalization in all patients and 6/9 patients had significant weight loss. Lab abnormalities included elevated CRP and Ferritin. Infectious work up showed Norovirus infection in 3 patients, Sapovirus in 1 and C difficile in 2 patients, however diarrhea persisted even after antimicrobial treatment. Abdominal imaging showed enterocolitis in one patient and pneumatosis in two patients. The most prominent endoscopic result was duodenal nodularity and villous blunting followed by non-specific erythema in the colon. Biopsy results showed a universal depletion of plasma cells, as well as increased lymphocyte infiltrate. Other findings include the presence of apoptosis and crypt dropout. Immunohistochemistry showed a predominantly CD4 population with one showing a CD4-positive T-cell lymphoproliferative disorder. Anti-microbial therapy was used in 3 patients, and parenteral nutrition in 5 patients. Management included IVIG (100%), Steroids (100%), bile acid sequestrants and Octreotide. Five of the nine patients received Biologics (Infliximab:3, Vedolizumab:2), however salvage therapy with Cyclophosphamide, Cyclosporine and Upadacitinib was used in one patient each. Three patients have died related to Myeloma or Parkinson related complications. Discussion: Enterocolitis is an uncommon and late consequence of CAR-T therapy and carries high morbidity and mortality. The small bowel is the most commonly and severely affected area. Duodenal biopsies can resemble autoimmune enteropathy and GVHD. Patients often require nutritional support, steroids, biologics or other immunosuppressants. These cases should be comanaged by Oncologists and Gastroenterologists.
Figure: Clinical features of IEC enterocolitis at index hospitalization.
