Association of antibiotic treatment with immune-related adverse events in patients with cancer receiving immunotherapy

Ying Jing; Xue Chen; Kunyan Li; Yaoming Liu; Zhao Zhang; Yiqing Chen; Yuan Liu; Yushu Wang; Steven H Lin; Lixia Diao; Jing Wang; Yanyan Lou; Douglas B Johnson; Xiang Chen; Hong Liu; Leng Han

doi:10.1136/jitc-2021-003779

Association of antibiotic treatment with immune-related adverse events in patients with cancer receiving immunotherapy

J Immunother Cancer. 2022 Jan;10(1):e003779. doi: 10.1136/jitc-2021-003779.

Authors

Ying Jing^#^{1

2}, Xue Chen^#³, Kunyan Li³, Yaoming Liu², Zhao Zhang², Yiqing Chen², Yuan Liu⁴, Yushu Wang², Steven H Lin⁵, Lixia Diao⁶, Jing Wang³, Yanyan Lou⁷, Douglas B Johnson⁸, Xiang Chen⁹, Hong Liu⁹, Leng Han^{10

4

11}

Affiliations

¹ Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
³ Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
⁴ Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas, USA.
⁵ Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁶ Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁷ Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁹ 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 leng.han@tamu.edu hongliu1014@csu.edu.cn chenxiangck@126.com.
¹⁰ Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA leng.han@tamu.edu hongliu1014@csu.edu.cn chenxiangck@126.com.
¹¹ Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX, USA.

^# Contributed equally.

Abstract

Background: To determine whether antibiotic treatment is a risk factor for immune-related adverse events (irAEs) across different patients with cancer receiving anti-PD-1/PD-L1 therapies.

Methods: The retrospective analysis includes clinical information from 767 patients with cancer treated at Hunan Cancer Hospital from 2017 to 2020. The pharmacovigilance data analysis includes individual cases of 38,705 safety reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2014 to 2020, and 25,122 cases of safety reports from the World Health Organization database VigiBase from 2014 to 2019. All cases that received anti-PD-1/PD-L1 treatment were included. Multiomics data from patients across 25 cancer types were download from The Cancer Genome Atlas. Logistic regression and propensity score algorithm was employed to calculate OR of irAEs.

Results: Retrospective analysis of in-house patients showed that irAE potential risks are higher in all cancer (OR 2.12, 95% CI 1.38 to 3.22, false discovery rate (FDR) adjusted-p=1.93×10^-3) and patients with lung cancer (OR 3.16, 95% CI 1.67 to 5.95, FDR adjusted-p=1.93×10^-3) when using antibiotics. Potential risk of irAEs in patients with lung cancer with antibiotic treatment is significantly higher in FAERS (OR 1.39, 95% CI 1.21 to 1.59; FDR adjusted-p=1.62×10^-5) and VigiBase (OR 1.32, 95% CI 1.09 to 1.59, FDR adjusted-p=0.05). Mechanistically, decreased microbial diversity caused by antibiotics use may increase the irAE risk through mediating the irAE-related factors.

Conclusions: Our study is the first to comprehensively demonstrate the associations of irAEs and antibiotic during anti-PD-1/PD-L1 therapy across a wide spectrum of cancers by analyzing multisource data. Administration of antibiotics should be carefully evaluated in patients with cancer treated by anti-PD-1/PD-L1 to avoid potentially increasing irAE risk.

Keywords: computational biology; immunotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Anti-Bacterial Agents / adverse effects*
Anti-Bacterial Agents / pharmacology
Drug-Related Side Effects and Adverse Reactions
Female
Humans
Immunotherapy / adverse effects
Male
Middle Aged
Neoplasms / complications*
Neoplasms / drug therapy*
Retrospective Studies

Substances

Anti-Bacterial Agents