S6120 Persistent Diarrhea Following CAR-T Therapy for Multiple Myeloma: A Case of Immune Effector Cell-Associated Enterocolitis

Introduction: Given the increasing number of patients receiving chimeric antigen receptor T-cell (CAR-T) therapy, it is important to be aware of potential gastrointestinal side effects of this treatment. We highlight a case of immune effector cell (IEC) enterocolitis following CAR-T therapy. Case Description/Methods: A 73-year-old woman with a history of IgG kappa multiple myeloma status post CAR-T with ciltacabtagene autoleucel was hospitalized 170 days after treatment for acute onset non-bloody diarrhea with >4 L stool per day. She was afebrile and hemodynamically stable. Labs were notable for hypokalemia, hypernatremia, acute kidney injury with creatinine 2.83 mg/dL (from baseline 1.19 mg/dL), albumin 3.4 g/dL. GI pathogen panel and C-diff were negative. Thyroid stimulating hormone, fecal calprotectin, fecal alpha-1 antitrypsin, celiac serologies, and 7AC4 were normal. Colonoscopy was grossly normal with biopsies negative for microscopic colitis or cytomegalovirus. Push enteroscopy demonstrated nodularity in the duodenum and jejunum. Small bowel aspirates were negative. Jejunal biopsies demonstrated villous blunting, crypt apoptosis, and patchy areas of increased intraepithelial lymphocytes with a predominance of CD4+ T-cells. Genetic analysis demonstrated clonal T-cell receptor gene arrangements. There was no evidence of mass or significant cytological atypia, making findings less consistent with a developing T-cell lymphoma. Her clinical presentation was most consistent with immune effector cell enterocolitis. She received intravenous methylprednisolone without significant improvement in her symptoms after 5 days, 1 dose of cyclophosphamide 1.5 mg/m2, and given ongoing diarrhea, received 2 doses of vedolizumab 300 mg intravenous, 1 week apart. Her diarrhea decreased and she discharged home. She was doing well at follow-up with 2-3 bowel movements per day. Discussion: IEC enterocolitis is a rare complication of CAR-T therapy, often presenting 1-3 months after infusion. Our patient had no evidence of colonic involvement, and the diagnosis was made based on small intestinal biopsies, highlighting that upper endoscopy with biopsies should be obtained when this condition is suspected. Biopsies demonstrate villous blunting and increased intraepithelial lymphocytes. This condition is treated with systemic corticosteroids, infliximab, or vedolizumab. Developing lymphoproliferative process should remain on the differential diagnosis, especially in patients not responding to treatment.