Background: Gastrointestinal (GI) immune-related adverse events (irAEs) commonly limit immune checkpoint inhibitors' (ICIs) treatment, which is very effective for metastatic melanoma. The independent impact of GI-irAEs on patients' survival is not well studied. We aimed to assess the impact of GI-irAEs on survival rates of patients with metastatic melanoma using multivariate model.
Methods: This is a retrospective study of patients with metastatic melanoma who developed GI-irAEs from 1/2010 through 4/2018. A number of randomized patients who did not have GI-irAEs were included as controls. Kaplan-Meier curves and log-rank test were used to estimate unadjusted survival durations. The Cox proportional hazards model was used to evaluate survival predictors; irAEs were included as time-dependent variables.
Results: A total of 346 patients were included, 173 patients had GI-irAEs; 124 (72%) received immunosuppression. In multivariate Cox regression, ECOG 2-3 (HR 2.57, 95%CI 1.44-4.57; P < 0.01), LDH ≥ 618 IU/L (HR 2.20, 95% CI 1.47-3.29; P < 0.01), stage M1c (HR 2.21, 95% CI 1.35-3.60; P < 0.01) were associated with worse OS rates. Any grade GI-irAEs (HR 0.53, 95% CI 0.36-0.78; P < 0.01) was associated with improved OS rates. Immunosuppressive treatment did not affect OS (P = 0.15). High-grade diarrhea was associated with improved OS (P = 0.04). Patients who developed GI-irAEs had longer PFS durations on Cox model (HR 0.56, 95% CI 0.41-0.76; P < 0.01).
Conclusion: GI-irAEs are associated with improved OS and PFS in patients with metastatic melanoma. Furthermore, higher grades of diarrhea are associated with even better patients' OS rates.
Keywords: Colitis; Diarrhea; Immune checkpoint inhibitors; Metastatic melanoma; Survival.