S3944 Case Series: Successful Treatment of Refractory Immune Checkpoint Inhibitor-Related Enterocolitis Using Risankizumab

Introduction: Immune checkpoint inhibitor-related enterocolitis (irEC) is a common complication of immune checkpoint inhibitors (ICI) and is typically managed with corticosteroids, infliximab, and vedolizumab. Limited data exist for additional therapies and the management of patients refractory to these agents. In this report, we present 3 patients treated with risankizumab (anti-IL23 therapy) for refractory irEC. Case Description/Methods: Case 1 is a woman in her 60s with metastatic renal cell carcinoma treated with lenvatinib and pembrolizumab developed grade 4 irEC affecting both the upper and lower gastrointestinal (GI) tracts 18 months into treatment. She experienced improvement with vedolizumab (3 doses) and infliximab (3 doses, including 2 at 10 mg/kg). But recurrent severe symptoms with fecal calprotectin (FCP) >1000 reaccurred, requiring multiple hospitalizations and prolonged total parenteral nutrition (TPN). She was switched to risankizumab 600 mg IV, showing improvement during induction. After 8 months of risankizumab, she achieved corticosteroid-free clinical remission with FCP reduced to 119 and was weaned off TPN. Case 2 is a woman in her 60s with locally advanced vaginal melanoma developed grade 3 irEC affecting the upper and lower GI tracts 2 months after starting ipilimumab and nivolumab. Corticosteroids and infliximab (2 doses at 10 mg/kg) provided inadequate control, with FCP increasing from 465 to 761. Risankizumab 600 mg IV was initiated due to severe enteritis, for which vedolizumab was considered less optimal. She showed improvement after the first dose, with FCP decreasing to 124 by the second dose. After completing 3 induction doses, she achieved corticosteroid-free clinical remission in 1 month. Case 3 is a woman in her 70s with bladder cancer treated with chemotherapy followed by a single dose of pembrolizumab developed grade 3 irEC affecting both upper and lower GI tracts within 1 week of initiation. Despite treatment with high-dose corticosteroids, infliximab (2 doses at 5 mg/kg), and vedolizumab (1 dose), she remained steroid-dependent with an FCP of 534. After transitioning to risankizumab 600 mg IV, she showed gradual improvement during induction and achieved corticosteroid-free clinical remission with normalization of FCP after 6 months. Discussion: This case series demonstrates the promising efficacy of risankizumab, a novel selective IL-23 inhibitor, in the treatment of severe irEC that involved both the upper and lower GI tracts and was refractory to multiple lines of therapy.