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

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

Publication date: Jul 09, 2019

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.

Hughes, Zheng, H., Zubiri, L., Molina, G.E., Chen, S.T., Mooradian, M.J., Allen, I.M., Reynolds, K.L., and Dougan, M. Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control. 23310. 2019 Cancer Med.

Concepts Keywords
Blockade Outcomes pharmaceutical use
Colitis Outcomes Hypoalbuminemia P
Common Hospitalization immunotherapy melanoma
Corticosteroid Charts melanoma 18years
Corticosteroids Immunosuppression
CPI Immunotherapy
Endoscopic Medicine
GEC Clinical medicine
Hypoalbuminemia Health
Immunosuppression Cancer treatments
Immunotherapy Immune system
Lactate Dehydrogenase Immunology
Lymphopenia Checkpoint inhibitor
Median Corticosteroid
Melanoma Immunotherapy
Morbidity Immunosuppression
Mortality Melanoma
Pharmaceutical Progression-free survival
Radiographic
Refractory
Symptom

Semantics

Type Source Name
pathway BSID Programmed Cell Death
gene UNIPROT CTLA4
disease DOID lymphopenia
disease MESH lymphopenia
disease MESH Hypoalbuminemia
disease MESH recrudescence
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID Colitis
disease MESH Colitis

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