Hamzah Abu-Sbeih1, Faisal S Ali1, Wei Qiao2, Yang Lu3, Sapna Patel4, Adi Diab4, Yinghong Wang5. 1. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA. 2. Department of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA. 3. Department of Nuclear Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA. 4. Department of Melanoma Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA. 5. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA. ywang59@mdanderson.org.
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.
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.
Authors: Austin R Thomas; Mostafa Eyada; Anusha S Thomas; Yinghong Wang; Miho Kono; Krishnavathana Varatharajalu; Yang Lu; Guofan Xu; Kavea Panneerselvam; Malek Shatila; Mehmet Altan; Jennifer Wang; John A Thompson; Hao Chi Zhang; Muhammad Ali Khan; Gottumukkala S Raju Journal: J Cancer Res Clin Oncol Date: 2022-10-15 Impact factor: 4.322
Authors: Hamzah Abu-Sbeih; Cynthia Nguyen Tran; Phillip S Ge; Manoop S Bhutani; Mazen Alasadi; Aung Naing; Amir A Jazaeri; Yinghong Wang Journal: J Immunother Cancer Date: 2019-05-03 Impact factor: 13.751