Nivolumab-associated DRESS in a genetic susceptible individual
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 afte...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2021-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/10/e002879.full |
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| author | Qian Li Yimei Wang Qing Liu Jie Gao Tianshu Liu Duojiao Wu Luoyan Ai Yuan Ji Shihai Zhao Yue-Hong Cui Xiaoshi Jin Jingjie Li Yiyi Yu |
| author_facet | Qian Li Yimei Wang Qing Liu Jie Gao Tianshu Liu Duojiao Wu Luoyan Ai Yuan Ji Shihai Zhao Yue-Hong Cui Xiaoshi Jin Jingjie Li Yiyi Yu |
| author_sort | Qian Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3d37d71db6874d35ac690debb0759c5f |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-3d37d71db6874d35ac690debb0759c5f2025-08-20T02:25:25ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-10-0191010.1136/jitc-2021-002879Nivolumab-associated DRESS in a genetic susceptible individualQian Li0Yimei Wang1Qing Liu2Jie Gao3Tianshu Liu4Duojiao Wu5Luoyan Ai6Yuan Ji7Shihai Zhao8Yue-Hong Cui9Xiaoshi Jin10Jingjie Li11Yiyi Yu12Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Nephrology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Gastroenterology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, ChinaCancer Center, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Pathology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Radiology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Nephrology, Zhongshan Hospital Fudan University, Shanghai, ChinaGenecast Biotechnology Co Ltd, Wuxi City, ChinaDepartment of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, ChinaThe 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.https://jitc.bmj.com/content/9/10/e002879.full |
| spellingShingle | Qian Li Yimei Wang Qing Liu Jie Gao Tianshu Liu Duojiao Wu Luoyan Ai Yuan Ji Shihai Zhao Yue-Hong Cui Xiaoshi Jin Jingjie Li Yiyi Yu Nivolumab-associated DRESS in a genetic susceptible individual Journal for ImmunoTherapy of Cancer |
| title | Nivolumab-associated DRESS in a genetic susceptible individual |
| title_full | Nivolumab-associated DRESS in a genetic susceptible individual |
| title_fullStr | Nivolumab-associated DRESS in a genetic susceptible individual |
| title_full_unstemmed | Nivolumab-associated DRESS in a genetic susceptible individual |
| title_short | Nivolumab-associated DRESS in a genetic susceptible individual |
| title_sort | nivolumab associated dress in a genetic susceptible individual |
| url | https://jitc.bmj.com/content/9/10/e002879.full |
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