An analysis of the effectiveness of specific guidelines for the management of ipilimumab-mediated diarrhea/colitis: Prevention of gastrointestinal perforation and/or colectomy

Abstract

9063 Background: The fully human, anti cytotoxic T lymphocyte antigen-4 monoclonal antibody ipilimumab (ipi) produced durable responses/stable disease in some patients (pts) with advanced melanoma. Ipi is associated with generally mild-moderate immune-related adverse events (irAEs), likely due to ipi’s mechanism of action and subsequent reduction in tolerance to self-antigens. In January 2005, diarrhea treatment guidelines (DTGs) were developed in cooperation with external experts - based on clinical experience - and introduced into all clinical trials with ipi (both ongoing and new). The guidelines called for close monitoring for any emergence/change in symptoms and prompt treatment of moderate-severe irAEs with corticosteroids. An analysis was conducted to determine if DTGs were effective in preventing life- threatening complications of diarrhea/colitis such as gastrointestinal (GI) perforation and/or colectomy. Methods: Historical safety data from early Medarex studies (which was mostly prior to implementation of the DTGs) was compared with that from ongoing BMS studies CA184004, -007,-008, and -022 (these studies had full DTG implementation). The GI perforation/colectomy rates, drug-related diarrhea, and serious GI irAEs were examined.Most pts in the early Medarex studies received 3 mg/kg ipi in various regimens while most ptss enrolled in ongoing BMS studies received 10 mg/kg ipi every 3 weeks (Q3W) X 4. Results: After the full implementation of DTGs, preliminary data show a substantial reduction (up to 50%) in GI perforation/colectomy rate despite an increase in ipi dose/exposure administered. Conclusions: Preliminary analysis suggests that DTGs are effective in reducing occurrence of life-threatening GI complications such as perforation/colectomy. Health-care providers should encourage pts to immediately report symptoms suggestive of colitis, utilize DTGs to reduce occurrence of life-threatening irAE GI complications, and adhere to treatment guidelines - appropriately treating moderate-severe GI- related irAEs with steroids to prevent serious complications. Education regarding irAE treatment may help to improve overall pts clinical outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex, Inc. Bristol-Myers Squibb, Medarex, Inc.