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

Authors
  • Hughes, Michael S1, 2
  • Zheng, Hui1, 2
  • Zubiri, Leyre1, 2
  • Molina, Gabriel E1, 2
  • Chen, Steven T1, 2, 3
  • Mooradian, Meghan J1, 2, 4
  • Allen, Ian M1, 2
  • Reynolds, Kerry L1, 2, 4
  • Dougan, Michael1, 2, 5
  • 1 Harvard Medical School, Boston, Massachusetts.
  • 2 Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
  • 3 Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts.
  • 4 Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
  • 5 Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
Type
Published Article
Journal
Cancer Medicine
Publisher
Wiley
Publication Date
Sep 01, 2019
Volume
8
Issue
11
Pages
4986–4999
Identifiers
DOI: 10.1002/cam4.2397
PMID: 31286682
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. 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. © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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