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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

Abstract

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

Metastatic melanoma Colitis Diarrhea Immune checkpoint inhibitors Survival 

Abbreviations

CI

Confidence interval

CT

Computed tomography

CTLA-4

Cytotoxic T-lymphocyte-associated protein 4

ECOG

Eastern Cooperative Oncology Group

FDA

Food and Drug Administration

FDG PET

Fluorodeoxyglucose positron emission tomography

GI

Gastrointestinal

HQROL

Health-related quality of life

HR

Hazard ratio

ICI

Immune checkpoint inhibitor

iCPD

Confirmed progressive disease

iCR

Immune complete response

IDC

Immune-mediated diarrhea and colitis

imRECIST

Immune-modified response evaluation criteria in solid tumors

iPR

Immune partial response

IQR

Interquartile range

irAE

Immune-related adverse event

iRECIST

Immune-related response evaluation criteria in solid tumors

iSD

Immune stable disease

iUPD

Immune unconfirmed progressive disease

LDH

Lactate dehydrogenase

OS

Overall survival

PD-1

Programmed cell death protein-1

PD-L1

Programmed death-ligand 1

PFS

Progression free survival

SD

Standard deviation

Notes

Acknowledgements

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.

Funding

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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