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

Cancer Med. 2019 Sep;8(11):4986-4999. doi: 10.1002/cam4.2397. Epub 2019 Jul 9.


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.

Keywords: CTLA-4; adverse effects; checkpoint inhibition; colitis; hospitalization; immunotherapy; melanoma; programmed cell death 1.

MeSH terms

  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Colitis / diagnosis*
  • Colitis / etiology*
  • Female
  • Hospitalization
  • Humans
  • Male
  • Melanoma / complications*
  • Melanoma / diagnosis
  • Melanoma / drug therapy
  • Molecular Targeted Therapy / adverse effects
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Severity of Illness Index


  • Antineoplastic Agents, Immunological