Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma
- 378 Downloads
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.
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.
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).
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.
KeywordsMetastatic melanoma Colitis Diarrhea Immune checkpoint inhibitors Survival
Cytotoxic T-lymphocyte-associated protein 4
Eastern Cooperative Oncology Group
Food and Drug Administration
- FDG PET
Fluorodeoxyglucose positron emission tomography
Health-related quality of life
Immune checkpoint inhibitor
Confirmed progressive disease
Immune complete response
Immune-mediated diarrhea and colitis
Immune-modified response evaluation criteria in solid tumors
Immune partial response
Immune-related adverse event
Immune-related response evaluation criteria in solid tumors
Immune stable disease
Immune unconfirmed progressive disease
Programmed cell death protein-1
Programmed death-ligand 1
Progression free survival
Medical editing of this paper was provided by the Department of Scientific Publications at MD Anderson Cancer Center.
HA-S: conceptualization, data curation, writing-original draft, methodology. FSA: writing-original draft, data curation. WQ: formal analysis, software, review and editing, methodology. YL: conceptualization, writing-review and editing, data curation. SP: conceptualization, writing-review and editing. AD: conceptualization, writing-review and editing, project administration, methodology. YW: conceptualization, writing-review and editing, project administration, methodology.
This study was not supported by any funding.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interests.
This retrospective, single-center study was approved by the Institutional Review Board at MD Anderson Cancer Center. Approval number: PA18-0472.
This study was granted waiver of consent.
- 1.Abu-Sbeih H et al (2018) Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma. J Immunother Cancer 6(Suppl 1):P537Google Scholar
- 24.Cox DR (1972) Regression models and life-tables. J R Stat Soc 34(2):187–220Google Scholar
- 25.Therneau TM, Grambsch PM (2000) Modeling survival data: extending the Cox model. Statistics for Biology and HealthGoogle Scholar
- 32.Horvat TZ et al (2015) Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol 33(28):3193–3198CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Schadendorf D et al (2017) Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events: a pooled analysis of randomized phase II and III trials. J Clin Oncol 35(34):3807–3814CrossRefPubMedPubMedCentralGoogle Scholar