Ying Jing1,2, Yongchang Zhang3, Jing Wang4, Kunyan Li4, Xue Chen4, Jianfu Heng4, Qian Gao5, Youqiong Ye1, Zhao Zhang1, Yaoming Liu1, Yanyan Lou6, Steven H Lin7, Lixia Diao8, Hong Liu5, Xiang Chen5, Gordon B Mills9, Leng Han1,10,11. 1. Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA. 2. Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 3. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. 4. Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China. 5. Department of Dermatology, Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Clinical Research Center for Cancer Immunotherapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. 6. Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA. 7. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 9. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. 10. Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA. 11. Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX, USA.
Abstract
BACKGROUND: Accumulated evidence supports the existence of sex-associated differences in immune systems. Understanding the role of sex in immune-related adverse events (irAEs) is important for management of irAE in patients receiving immunotherapy. METHODS: We performed meta-analysis on published clinical study data and multivariable logistic regression on pharmacovigilance data and applied a propensity algorithm to The Cancer Genome Atlas omics data. We further validated our observations in 2 independent in-house cohorts of 179 and 767 cancer patients treated with immune checkpoint inhibitors. RESULTS: A meta-analysis using 13 clinical studies that reported on 1096 female patients (36.8%, 95% confidence interval [CI] = 35.0% to 38.5%) and 1886 male patients (63.2%, 95% CI = 61.5% to 65.0%) demonstrated no statistically significant irAE risk difference between the sexes (odds ratio [OR] = 1.19, 95% CI = 0.91 to 1.54, 2-sided P = .21). Multivariable logistic regression analysis of 12 225 patients from the Food and drug administration Adverse Event Reporting System (FAERS) and 10 979 patients from VigiBase showed no statistically significant difference in irAEs by sex. A propensity score algorithm used on multi-omics data for 6019 patients from The Cancer Genome Atlas found no statistically significant difference by sex for irAE-related factors or pathways. The retrospective analysis of 2 in-house patient cohorts validated these results (OR = 1.55, 95% CI = 0.98 to 2.47, false discovery rate = 0.13, for cohort 1; OR = 1.16, 95% CI = 0.86 to 1.57, false discovery rate = 0.39, for cohort 2). CONCLUSIONS: We observed minimal sex-associated differences in irAEs among cancer patients who received immune checkpoint inhibitor therapy. It may be unnecessary to consider sex effects for irAE management in clinical practice.
BACKGROUND: Accumulated evidence supports the existence of sex-associated differences in immune systems. Understanding the role of sex in immune-related adverse events (irAEs) is important for management of irAE in patients receiving immunotherapy. METHODS: We performed meta-analysis on published clinical study data and multivariable logistic regression on pharmacovigilance data and applied a propensity algorithm to The Cancer Genome Atlas omics data. We further validated our observations in 2 independent in-house cohorts of 179 and 767 cancer patients treated with immune checkpoint inhibitors. RESULTS: A meta-analysis using 13 clinical studies that reported on 1096 female patients (36.8%, 95% confidence interval [CI] = 35.0% to 38.5%) and 1886 male patients (63.2%, 95% CI = 61.5% to 65.0%) demonstrated no statistically significant irAE risk difference between the sexes (odds ratio [OR] = 1.19, 95% CI = 0.91 to 1.54, 2-sided P = .21). Multivariable logistic regression analysis of 12 225 patients from the Food and drug administration Adverse Event Reporting System (FAERS) and 10 979 patients from VigiBase showed no statistically significant difference in irAEs by sex. A propensity score algorithm used on multi-omics data for 6019 patients from The Cancer Genome Atlas found no statistically significant difference by sex for irAE-related factors or pathways. The retrospective analysis of 2 in-house patient cohorts validated these results (OR = 1.55, 95% CI = 0.98 to 2.47, false discovery rate = 0.13, for cohort 1; OR = 1.16, 95% CI = 0.86 to 1.57, false discovery rate = 0.39, for cohort 2). CONCLUSIONS: We observed minimal sex-associated differences in irAEs among cancer patients who received immune checkpoint inhibitor therapy. It may be unnecessary to consider sex effects for irAE management in clinical practice.
Authors: Nicholas S Wilcox; Seth J Rotz; McKay Mullen; Evelyn J Song; Betty Ky Hamilton; Javid Moslehi; Saro H Armenian; Joseph C Wu; June-Wha Rhee; Bonnie Ky Journal: Circ Res Date: 2022-02-17 Impact factor: 17.367
Authors: Ajay Sheshadri; Alberto A Goizueta; Vickie R Shannon; David London; Guillermo Garcia-Manero; Hagop M Kantarjian; Farhad Ravandi-Kashani; Tapan M Kadia; Marina Y Konopleva; Courtney D DiNardo; Sherry Pierce; Abdulrazzak Zarifa; Aya A Albittar; Linda L Zhong; Fechukwu O Akhmedzhanov; Muhammad H Arain; Mansour Alfayez; Ahmad Alotaibi; Mehmet Altan; Aung Naing; Tito R Mendoza; Myrna C B Godoy; Girish Shroff; Sang T Kim; Saadia A Faiz; Dimitrios P Kontoyiannis; Fareed Khawaja; Kristofer Jennings; Naval G Daver Journal: Cancer Date: 2022-04-22 Impact factor: 6.921