Effectiveness of treatment guidance on diarrhea and colitis across ipilimumab studies.

8554 Background: Ipilimumab is a fully human monoclonal antibody that potentiates immunity by blocking interactions between CTLA-4 and CD80/CD86. Ipilimumab has shown survival benefit in subjects with previously treated metastatic melanoma (Hodi et al, NEJM 2010;363:711). Diarrhea/colitis (D/C) are adverse events that occur with ipilimumab which could develop into serious life threatening complications such as bowel perforation. A gastrointestinal management guideline has been developed as a reference for managing D/C events. The objective of this analysis was to assess the effectiveness of a protocol specified treatment algorithm on the management of D/C. Methods: This was an event level analysis. A total of 687 D/C events from 5 studies in which 511 subjects received ipilimumab 3 mg/kg every 3 wks for 4 doses, and 325 subjects received 10 mg/kg. Results: Subjects in the 3 mg/kg cohort reported 370 D/C events. Guidance for Grade 1 (g1) diarrhea was to treat symptomatically without immunosuppressives (IS) unless it persisted beyond 5 days: 64% of the events were g1, 18% prompted treatment with IS. Of the g1 events that were managed with IS, 67% resolved; of those that did not receive IS, 87% resolved. Guidance for g2 diarrhea was to treat symptomatically, with budesonide, or with corticosteroids if symptoms persist for 3-5 days or worsen. G2 D/C occurred in 22% of all events; 46% were treated with IS; median time to first IS was 3 days. The majority of g2 events resolved or improved regardless of IS. Systemic corticosteroids were recommended for g≥3 D/C. Resolution/downgrading of symptoms occurred in 90% of g≥3 events after IS. Median time to resolution was 2 wks and median time to downgrade was 1 wk. Initiation of IS within 5 days from onset of an event led to faster resolution of symptoms compared to IS after 5 days. 13% of the events were g≥3; 86% were managed with systemic corticosteroids and median time to first dose was 1 day. Conclusions: When the use of protocol specified guidance was followed appropriately it led to resolution of D/C during ipilimumab treatment. The majority of high grade colitis events were treated with systemic steroids. Rapid institution of IS (within 5 days) led to faster resolution of symptoms.