Abstract
INTRODUCTION: Background Immune-mediated diarrhea and colitis (IMDC) is the second most common immune-related adverse effect related to immune checkpoint inhibitor (ICI) therapy. In this study, we aimed to identify risk factors for chronic IMDC and the prognostic value of chronic IMDC in terms of cancer outcome. METHODS: We retrospectively reviewed the charts of all patients with an established diagnosis of IMDC over a study period from January, 2018, through October, 2019, and grouped them, based on duration of disease, into acute (≤3 months) and chronic ( >3 months) IMDC categories. Patient demographics, clinical variables, and overall survival (OS) data were collected. A logistic regression model was used to assess the factors associated with chronic IMDC. The Kaplan-Meier and log-rank tests were used to estimate and compare OS differences between the two groups. RESULTS: Our sample was comprised of 88 patients, with 43 in the chronic IMDC, and 45 in the acute IMDC group. Median age was 65.5 years at the time of IMDC. Genitourinary cancer and melanoma accounted for 70% of malignancies in our cohort. PD-1/L1 monotherapy (52%) was more frequently used than CTLA-4 monotherapy (17%) or combination therapy (31%). Our analysis demonstrated that chronic IMDC was associated with PPI use (OR = 3.96, P = 0.026), long duration of IMDC symptoms (OR = 1.05, P < 0.001) and hospitalization (OR = 1.065, P = 0.043), histological feature of chronic active colitis (OR = 4.8, P = 0.025) or microscopic colitis (OR = 5.0, P = 0.045) and delayed introduction of SIT for IMDC (OR = 1.06, P = 0.047). Our results also demonstrated that chronic IMDC reflected a better cancer response to ICIs (30% vs. 51%, P = 0.002) and is accompanied by improved OS (P = 0.035). Similarly, we observed that high doses of SIT were associated with better OS (P = 0.018). CONCLUSION: Chronic IMDC can develop among patients with more aggressive IMDC disease course and chronic features on colon histology. It likely reflects a prolonged ICI effect, therefore is associated with a better cancer outcome and overall survival. Optimization of IMDC treatment target should be considered to improve treatment outcome in the future.Figure 1Figure 2.: Kaplan-Meier OS curve, stratified by patient. (A) OS duration between the chronic IMDC (>3 months) and acute IMDC groups (≤3 months). (B) OS duration in cases with 1–2 doses of SIT (infliximab or vedolizumab) vs. ≥3 doses of SIT.Table 1
Published Version
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