Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections

Lu, Minya; Li, Yue; Wang, Hanping; Guo, Xiaoxiao; Zhou, Jiaxin; Duan, Lian; Si, Xiaoyan; Xu, Yingchun; Zhang, Li

doi:10.1111/1759-7714.13313

Cited by 8 publications

(8 citation statements)

References 36 publications

(83 reference statements)

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“…Several studies showed that mice with PD1 deletion appear to have significantly increased proinflammatory cytokines, resulting in excessive inflammation, and therefore uncontrolled bacterial growth [9]. A boost of T helper cell TH1 function is another possible explanation and can be compared to the immune reconstitution inflammatory syndrome (IRIS) in HIV patients [10]. The same reasoning can be applied to T. gondii infections.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bilateral Severe Panuveitis Occurring during Cancer Immunotherapy with Dabrafenib and Trametinib Therapy Due to Toxoplasmosis Reactivation

Hsin

Stappler

Schalenbourg

et al. 2023

Klin Monbl Augenheilkd

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Section: Discussionmentioning

confidence: 99%

“…However, other studies must be conducted because of divergent results. Indeed, some studies have noted that enhancement of the T cell by PD-1/PD-L1 blockage can lead to pathogen elimination [10]. Indeed, chronic infection induces CD8+ T cell exhaustion via the PD1-PDL-1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Bilateral Severe Panuveitis Occurring during Cancer Immunotherapy with Dabrafenib and Trametinib Therapy Due to Toxoplasmosis Reactivation

Hsin

Stappler

Schalenbourg

et al. 2023

Klin Monbl Augenheilkd

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“…50 Moreover, reactivation of latent infections, such as tuberculosis, has also been described. 51 In addition, in the time of coronavirus disease 2019 pandemic, severe acute respiratory syndrome coronavirus 2 infection should be considered in case of new-onset pulmonary changes detected 2. Rhinovirus bronchiolitis during maintenance therapy with nivolumab in a 64-year-old woman with metastatic melanoma.…”

Section: Differential Diagnosismentioning

confidence: 99%

“…Opportunistic infection represents the most important complication of irAEs and is often owing to the steroid, immunosuppressive or immunomodulatory, treatment required to control the disease 18,51 (Fig. 10).…”

Section: Complicationsmentioning

confidence: 99%

Imaging Features of Pulmonary Immune-related Adverse Events

Pozzessere

Lazor

Jumeau

et al. 2021

Journal of Thoracic Oncology

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Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.

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“…However, when irAEs set in that require additional immunosuppressive therapy with high-dose corticosteroid and/or other biologic or non-biologic immunosuppressants, the risk of invasive fungal disease is significantly increased. Some authors have recommended routine pretreatment screening for latent/chronic infections such as latent tuberculosis and viral hepatitis, 93 but there is a lack of evidence support, and it is unclear whether the screening strategy should be generalized to involve opportunistic fungal infection, e.g., histoplasmosis. Apart from the established guideline on PJP prophylaxis in patients treated with prolonged high-dose corticosteroid, the role of antibacterial, antifungal, and/or antiviral prophylaxis in patients receiving immune checkpoint blocking agents requires further evaluation.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Fungal infection risks associated with the use of cytokine antagonists and immune checkpoint inhibitors

Lau

Woo

2020

Exp Biol Med (Maywood)

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The revolutionary success of biologic agents in treating various malignant and autoimmune conditions has been met with increased risk of opportunistic infections due to perturbations in immunity. In patients receiving biologic-containing regimens, the risk of fungal infection is less well-understood, and there is a lack of established guideline on the standard of care in terms of screening and prophylaxis. In this article, we reviewed the risk of fungal infections associated with cytokine antagonists, including anti-tumor necrosis factor (TNF) agents and interleukin (IL) antagonists, and immune checkpoint inhibitors. The risk of fungal infection in this group of patients is drug-, pathogen-, host-, and context-dependent. Among the biologic agents reviewed, anti-TNF agents are associated with highest number of reported cases of fungal infection, especially histoplasmosis. In fact, infection due to all dimorphic fungi except Talaromyces marneffei have been reported in patients receiving TNF-α inhibitors, despite their widespread use in T. marneffei-endemic regions. The risk is higher with TNF-α inhibitors that block both the membrane-bound and soluble forms of TNF-α, i.e., infliximab and adalimumab, compared with etanercept which inhibits the soluble form only. In addition to the preferential suppression of Th1 pathway and granuloma formation leading to genuinely higher risk of infection, the longer history and extensive use of infliximab coupled with the endemicity of histoplasmosis in the United States lead to an apparent increase in reported cases. IL-17 antagonists lead to a moderate increase in mucocutaneous candidiasis, but not the risk of life-threatening mycosis, consistent with the essential role of Th17 cells in mucosal defense. Immune checkpoint inhibitors, on the other hand, do not significantly increase the risk of invasive fungal infections when used alone and may even be of therapeutic value in the treatment of severe and refractory mycosis. Impact statement The risk of opportunistic infections due to fungi is relatively less well addressed in patients receiving biologic agents, compared with other opportunistic bacterial and viral infections. There is a lack of consensus guideline on the screening, prophylaxis, and management of fungal infection in patients anticipated to receive or actively receiving biologic therapy. In addition, invasive mycosis in immunocompromised patients is associated with high mortality and morbidity. This review highlighted the risk of fungal infection in patients receiving cytokine antagonists and immune checkpoint inhibitors, two big categories of biologic agents that are widely used in the treatment of various autoimmune and malignant conditions, often in combination with other immunomodulatory or immunosuppressive agents but also as standalone therapy. The adverse outcomes of opportunistic fungal infection in these patients can be reduced by heightened awareness, active case finding, and prompt treatment.

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Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections

Cited by 8 publications

References 36 publications

Bilateral Severe Panuveitis Occurring during Cancer Immunotherapy with Dabrafenib and Trametinib Therapy Due to Toxoplasmosis Reactivation

Bilateral Severe Panuveitis Occurring during Cancer Immunotherapy with Dabrafenib and Trametinib Therapy Due to Toxoplasmosis Reactivation

Imaging Features of Pulmonary Immune-related Adverse Events

Fungal infection risks associated with the use of cytokine antagonists and immune checkpoint inhibitors

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