TY - JOUR
T1 - Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma
AU - Abu-Sbeih, Hamzah
AU - Ali, Faisal S.
AU - Qiao, Wei
AU - Lu, Yang
AU - Patel, Sapna
AU - Diab, Adi
AU - Wang, Yinghong
N1 - Funding Information:
Medical editing of this paper was provided by the Department of Scientific Publications at MD Anderson Cancer Center.
Funding Information:
Acknowledgements Medical editing of this paper was provided by the Department of Scientific Publications at MD Anderson Cancer Center.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/4/2
Y1 - 2019/4/2
N2 - 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.
AB - 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.
KW - Colitis
KW - Diarrhea
KW - Immune checkpoint inhibitors
KW - Metastatic melanoma
KW - Survival
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U2 - 10.1007/s00262-019-02303-1
DO - 10.1007/s00262-019-02303-1
M3 - Article
C2 - 30666357
AN - SCOPUS:85060351432
SN - 0340-7004
VL - 68
SP - 553
EP - 561
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 4
ER -