Cancer Immunology, Immunotherapy

, Volume 68, Issue 4, pp 553–561 | Cite as

Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma

  • Hamzah Abu-Sbeih
  • Faisal S. Ali
  • Wei Qiao
  • Yang Lu
  • Sapna Patel
  • Adi Diab
  • Yinghong WangEmail author
Original Article



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.


Metastatic melanoma Colitis Diarrhea Immune checkpoint inhibitors Survival 



Confidence interval


Computed tomography


Cytotoxic T-lymphocyte-associated protein 4


Eastern Cooperative Oncology Group


Food and Drug Administration


Fluorodeoxyglucose positron emission tomography




Health-related quality of life


Hazard ratio


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


Interquartile range


Immune-related adverse event


Immune-related response evaluation criteria in solid tumors


Immune stable disease


Immune unconfirmed progressive disease


Lactate dehydrogenase


Overall survival


Programmed cell death protein-1


Programmed death-ligand 1


Progression free survival


Standard deviation



Medical editing of this paper was provided by the Department of Scientific Publications at MD Anderson Cancer Center.

Author contributions

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.

Ethical approval

This retrospective, single-center study was approved by the Institutional Review Board at MD Anderson Cancer Center. Approval number: PA18-0472.

Informed consent

This study was granted waiver of consent.

Supplementary material

262_2019_2303_MOESM1_ESM.pdf (269 kb)
Supplementary material 1 (PDF 268 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology, Hepatology and NutritionThe University of Texas, MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of BiostatisticsThe University of Texas, MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Nuclear MedicineThe University of Texas, MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Melanoma Medical OncologyThe University of Texas, MD Anderson Cancer CenterHoustonUSA

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