Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

• Main Authors: Michael S. Hughes, Hui Zheng, Leyre Zubiri, Gabriel E. Molina, Steven T. Chen, Meghan J. Mooradian, Ian M. Allen, Kerry L. Reynolds, Michael Dougan
• Format: Article
• Language: English
• Published: Wiley 2019-09-01
• Series: Cancer Medicine
• Subjects: adverse effects; checkpoint inhibition; colitis; CTLA‐4; hospitalization; immunotherapy
• Online Access: https://doi.org/10.1002/cam4.2397

Abstract Background Immune checkpoint inhibitors (CPIs) have revolutionized oncologic therapy but can lead to immune‐related adverse events (irAEs). Corticosteroids are first‐line treatment with escalation to biologic immunosuppression in refractory cases. CPI‐related gastroenterocolitis (GEC) affects 20%‐50% of patients receiving CPIs and can carry significant morbidity and mortality. Severe CPI‐related GEC is not well‐described. We present the clinical characterization of all CPI‐related GEC requiring admission at a single institution. Methods Clinical, laboratory, radiographic, and endoscopic data were extracted from charts of all melanoma patients ≥18 years of age admitted to one institution for CPI‐related GEC, from February 5, 2011 to December 13, 2016. Patients were followed until December 31, 2017 for further admissions. Survival, outcomes, and pharmaceutical‐use analyses were performed. Results Median time‐to‐admission from initial CPI exposure was 73.5 days. Median length of stay was 4.5 days. About 50.0% required second‐line immunosuppression. Readmission for recrudescence occurred in 33.3%. Common Terminology Criteria for Adverse Events (CTCAE) grade was not significantly associated with outcomes. Hypoalbuminemia (P = 0.005), relative lymphopenia (P = 0.027), and decreased lactate dehydrogenase (P = 0.026) were associated with second‐line immunosuppression. There was no difference in progression‐free survival (PFS) or OS (P = 0.367, 0.400) for second‐line immunosuppression. Subgroup analysis showed that early corticosteroid administration (P = 0.045) was associated with decreased PFS. Conclusions Severe CPI‐related GEC typically manifests within 3 months of immunotherapy exposure. Rates of second‐line immunosuppression and readmission for recrudescence were high. CTCAE grade did not capture the degree of severity in our cohort. Second‐line immunosuppression was not associated with poorer oncologic outcomes; however, early corticosteroid exposure was associated with decreased PFS. Further investigation is warranted.