Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) are gaining increasing popularity as an efficacious treatment for advanced malignancies. ICPI treatment can be complicated by diarrhea and colitis. Systemic steroids are the first line treatment. Infliximab is reserved for severe refractory cases. We aimed to assess the impact of ICPI-induced diarrhea and colitis and their immunosuppressive treatment on patients' outcomes. METHODS: This retrospective analysis was conducted in 327 cancer patients who received ICPIs between 2011 and 2017. Patients with ICPI-induced toxicities in other organs were excluded. We collected data about patient demographics, clinical variables, and overall survival. We used descriptive analysis to compare different groups based on the occurrence and the treatment of diarrhea and colitis. Kaplan-Meier and log-rank test were used to estimate and compare overall survival durations between groups. RESULTS: Diarrhea was recorded in 117 (36%) patients; 79 (24%) of them required immunosuppressive treatment of either systemic corticosteroid without infliximab (n = 44) or with infliximab (n = 35). Caucasian ethnicity, melanoma, stage 3 cancer, and ipilimumab were predictors of colitis that requires immunosuppression. Patients who required immunosuppressants had better overall survival than those who did not require treatment for colitis or diarrhea (P < 0.001). Immunosuppression for diarrhea or colitis did not affect the overall survival significantly (P = 0.232), nor did the choice of treatment (corticosteroids with vs. without infliximab; P = 0.768). Diarrhea was an independent predictor of a favorable overall survival (P < 0.001), irrespective of treatment need (P = 0.003). We confirmed the same results in a subgroup analysis for patients with stage IV malignancies only. Patients who received long duration of steroid treatment (> 30 days) had numerically higher infection rate than those who received steroid for shorter duration (40.4 vs. 25.8%, P = 0.160). Likewise, long duration of steroid without infliximab was associated with increased risk of infection compared to short duration of steroid with infliximab (42.9% vs. 14.3%, P = 0.089). CONCLUSIONS: Patients with ICPI-induced diarrhea or colitis have improved survival outcomes. Diarrhea is an independent predictor of an improved survival regardless of treatment requirement. Immunosuppressive treatment for diarrhea did not significantly affect overall survival, however, infection rates were numerically higher among patients who received steroids for a long duration. Therefore, early non-steroid immunosuppressive therapy may ensure a more favorable overall outcome.

Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis.

Background: Diarrhea and colitis are the second most common immune checkpoint inhibitor (ICPI)-induced adverse events. However, a comprehensive characterization of the endoscopic and histologic features of ICPI-induced diarrhea and colitis is lacking. Therefore, we aimed to describe endoscopic and histologic features of ICPI-induced gastrointestinal toxicities and to assess their association with patients' clinical characteristics and outcomes. Methods: We retrospectively reviewed records of 53 patients with ICPI-related diarrhea/colitis between 2011 and 2017. We collected data on demographics, diarrhea/colitis grade, treatment, and endoscopic and histologic findings. Long-term follow-up included repeat endoscopy findings, diarrhea recurrence, and overall survival. We compared groups by treatment, endoscopic and histologic findings, and constructed Kaplan-Meier survival curves. Results: Most patients had grade 2 or higher diarrhea (87%) and colitis (60%). Thirty-one patients were successfully treated with corticosteroids, and 22 additionally required infliximab. On endoscopy, 21 (40%) patients had ulcerations and 22 (42%) had nonulcerative inflammation. Patients with ulcerations had more steroid-refractory disease (P = 0.044) and high-grade diarrhea (P = 0.033). Histology showed mostly acute (23%) or chronic (60%) inflammation. During mean follow-up duration of 18.9 months, 19 (36%) developed recurrent diarrhea. Most patients had persistent endoscopic (8/13, 62%) and histologic (9/11, 82%) inflammation. Patients with higher-grade adverse events had improved survival. Higher-grade colitis was associated with endoscopic inflammation (P = 0.039), but grade of diarrhea was not associated with endoscopic inflammation or grade of colitis. Conclusion: 10.1093/ibd/izy104_video1izy104.video15808053084001.