Abstract
BackgroundImmune 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.MethodsClinical, 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.ResultsMedian 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.ConclusionsSevere 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.
Highlights
Immune checkpoint inhibitors (CPIs) have revolutionized cancer therapy over the past decade.[1,2] CPIs are clinically associated with durable responses in a wide range of cancers, including those of any origin with microsatellite instability or mismatch‐repair deficiencies, and the use of CPIs is rapidly growing.[3-7]
The severity and spectrum of immune‐related adverse events (irAEs) are related to the specific pathway targeted, with inhibition of cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) generally having more frequent and more severe irAEs compared to inhibitors of programmed cell death‐1 (PD‐1) or its ligand (PD‐L1).[1]
We identified all patients ≥18 years of age with stage III/IV melanoma hospitalized at Massachusetts General Hospital for expert‐confirmed CPI‐related GEC from February 05, 2011 to December 13, 2016; patients were followed for further admissions until December 31, 2017 (MGH Research Patient Data Registry)
Summary
Immune checkpoint inhibitors (CPIs) have revolutionized cancer therapy over the past decade.[1,2] CPIs are clinically associated with durable responses in a wide range of cancers, including those of any origin with microsatellite instability or mismatch‐repair deficiencies, and the use of CPIs is rapidly growing.[3-7]. CPIs are clinically associated with durable responses in a wide range of cancers, including those of any origin with microsatellite instability or mismatch‐repair deficiencies, and the use of CPIs is rapidly growing.[3-7] This novel class of agents enhances adaptive immune responses to cancer through inhibition of major T‐ lymphocyte coinhibitory pathways that otherwise block “immune escape” mechanisms.[2]. One of the most important factors complicating management of CPI‐related GEC is whether a patient responds to first‐line corticosteroids, and predictors of the need for second‐line immune suppression are of considerable clinical interest. We aimed to clinically characterize CPI‐related GEC requiring hospitalization in a retrospective cohort study, focusing on clinical factors that are associated with the requirement for secondary immune suppression
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