PMID- 34599025 OWN - NLM STAT- MEDLINE DCOM- 20220111 LR - 20220111 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 9 IP - 10 DP - 2021 Oct TI - Nivolumab-associated DRESS in a genetic susceptible individual. LID - 10.1136/jitc-2021-002879 [doi] LID - e002879 AB - The use of immune checkpoint inhibitors (ICIs) is rising exponentially in numerous cancers, but immune-related adverse events can occur. We report a rare case of high-grade drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome developed stepwise in a patient with gastric cancer after nivolumab treatment. Subclinical myocarditis was sensitively detected by cardiovascular magnetic resonance 3 weeks after initiating nivolumab. Eruption, eosinophilia, and interstitial pneumonitis occurred 1 week later. Corticosteroids were started and his condition improved. Four months later, when he was still on steroids tapering off, acute kidney injury and sequential herpes zoster virus activation developed. Severe acute tubulointerstitial nephritis (ATN) with an intense infiltration of lymphocytes was observed on renal biopsy. In blood, a substantial shift to Th2 response, an increase of Th17 cells, and strikingly enriched granzyme B(+) and perforin(+) CD8(+) T cells were detected at ATN onset. Serum interleukin (IL)-5, IL-17, interferon gamma, and IL-6 levels were consistently elevated. Further molecular profiling identified a DRESS risk allele human leukocyte antigen (HLA)-A*31:01 in this patient. His ATN responded favorably to a high dose of corticosteroids. In parallel, complete antitumor response was observed during the clinical course of DRESS. This is the first ever case report of nivolumab-associated DRESS syndrome with exploration of the mechanisms from the histopathological, cellular and molecular aspects. Nivolumab-induced DRESS may result from type IV hypersensitivity-related 'off-target effect' and PD-1 block-mediated 'on-target effect'. HLA risk alleles may constitute the genetic susceptible basis. HLA typing assay has the potential to screen susceptible individuals to avoid ICI-induced DRESS. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Ai, Luoyan AU - Ai L AUID- ORCID: 0000-0002-1093-2018 AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Gao, Jie AU - Gao J AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Zhao, Shihai AU - Zhao S AD - Department of Radiology, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Li, Qian AU - Li Q AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Cui, Yue-Hong AU - Cui YH AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Liu, Qing AU - Liu Q AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Wu, Duojiao AU - Wu D AUID- ORCID: 0000-0003-2562-8825 AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Wang, Yimei AU - Wang Y AD - Department of Nephrology, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Jin, Xiaoshi AU - Jin X AD - Department of Nephrology, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Ji, Yuan AU - Ji Y AD - Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Li, Jingjie AU - Li J AD - Genecast Biotechnology Co Ltd, Wuxi City, China. FAU - Yu, Yiyi AU - Yu Y AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China liu.tianshu@zs-hospital.sh.cn Yu.yiyi@zs-hospitsl.sh.cn. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. FAU - Liu, Tianshu AU - Liu T AD - Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China liu.tianshu@zs-hospital.sh.cn Yu.yiyi@zs-hospitsl.sh.cn. AD - Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Immune Checkpoint Inhibitors) RN - 31YO63LBSN (Nivolumab) SB - IM MH - Aged MH - Drug Hypersensitivity Syndrome/*etiology MH - Eosinophilia/*chemically induced MH - Genetic Predisposition to Disease/*etiology MH - Humans MH - Immune Checkpoint Inhibitors/*adverse effects MH - Male MH - Nivolumab/*adverse effects MH - Syndrome PMC - PMC8488716 OTO - NOTNLM OT - DRESS OT - HLA OT - Nivolumab OT - type IV hypersensitivity COIS- Competing interests: None declared. EDAT- 2021/10/03 06:00 MHDA- 2022/01/12 06:00 PMCR- 2021/10/01 CRDT- 2021/10/02 05:34 PHST- 2021/07/16 00:00 [accepted] PHST- 2021/10/02 05:34 [entrez] PHST- 2021/10/03 06:00 [pubmed] PHST- 2022/01/12 06:00 [medline] PHST- 2021/10/01 00:00 [pmc-release] AID - jitc-2021-002879 [pii] AID - 10.1136/jitc-2021-002879 [doi] PST - ppublish SO - J Immunother Cancer. 2021 Oct;9(10):e002879. doi: 10.1136/jitc-2021-002879.