Diagnosis and management of immune effector cell-associated enterocolitis (IEC-EC) following ciltacabtagene autoleucel

Immune effector cell-associated enterocolitis (IEC-EC) has been observed after ciltacabtagene autoleucel (cilta-cel, Carvykti) CAR-T. It is associated with dismal outcomes and is poorly characterized. Here, we examined its clinical features, risk factors and proposed management strategies. Among 229 consecutive patients who received cilta-cel at Mayo Clinic, 9 (3.9%) patients presented with a non-resolving, non-bloody, grade 3 diarrhea, often requiring prolonged total parenteral nutrition (TPN). Gastrointestinal coinfections were seen in the majority of cases. Median time from CAR-T infusion to symptom onset was 85 days (range 35-166) and there appeared to be a latency from symptom onset to endoscopic evaluation. Histopathology findings resembling graft-versus-host disease pattern of mucosal injury were most seen on duodenal biopsies whilst two cases had patterns akin to a T-cell lymphoproliferative disorder (one CD4+ and one CD8+). Independent associated factors for IEC-EC included high-risk disease as defined by the IMS/IMWG, prolonged cytokine release syndrome and antecedent delayed neurotoxicity. Response to first-line therapy comprising intravenous or oral corticosteroids, bile acid sequestrants, intravenous immunoglobulin and anti-microbial directed therapy was poor with no durable responses. Biologic therapy appeared to induce durable responses in 3/5 pts (2/2 vedolizumab, 1/3 infliximab); none of the responders had gastrointestinal co-infection. Early gastroenterology input for endoscopic evaluation with the inclusion of duodenal biopsy is a key component for diagnosis. Early institution of biologic therapy after failure of a short course of corticosteroids should be considered.