Treatment of corticosteroid refractory immune checkpoint inhibitor myocarditis with Infliximab: a case series

Zhang, Robert; Padegimas, Allison; Murphy, Kathleen M.; Evans, Peter T.; Peters, Carli J.; Domenico, Christopher; Vidula, Mahesh K.; Mather, Paul; Cevasco, Marisa; Cohen, Roger B.; Carver, Joseph R.; O’Quinn, Rupal

doi:10.1186/s40959-021-00095-x

Cited by 22 publications

(18 citation statements)

References 32 publications

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“…There is relatively sufficient evidence for infliximab in the treatment of steroid-refractory colitis ( 5 , 14 ). However, results are ambiguous for infliximab in the treatment of steroid-refractory CIP, also includes myocarditis ( 16 , 17 ). Some data about infliximab in steroid-refractory CIP are positive ( 18 ), but others are opposite.…”

Section: Discussionmentioning

confidence: 99%

Infliximab in the treatment of tislelizumab-induced steroid-refractory immune checkpoint inhibitor-related pneumonia: case report and literature review

Chen¹,

He²

2022

Transl Cancer Res TCR

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Background: Infliximab has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for the treatment of steroid-refractory immune checkpoint inhibitor-related pneumonia (CIP), but clinical evidence remains insufficient. In order to improve the level of diagnosis and treatment and rational use of infliximab in the treatment of CIP, a successful case is reported and the relevant literature is reviewed.Case Description: We report a 67-year-old male patient with small cell lung cancer (SCLC) who was admitted to hospital with rapidly worsening dyspnea and bilateral interstitial lung following PD-1 inhibitor (tislelizumab) combined with chemotherapy and radiation therapy. According to the comprehensive judgment of the patient's medical history, clinical symptoms, imaging manifestations, laboratory tests, exclusion of infection, heart failure and treatment response, the diagnosis of grade 4 CIP was made. The patient's condition did not improve after high-dose glucocorticoid and immunoglobulin therapy. After infliximab was added, the clinical manifestations and imaging were significantly improved, oxygenation index also gradually return to normal, then the patient was discharged smoothly.Conclusions: This report suggests that infliximab should be considered when high-dose glucocorticoids combined with immunoglobulin are ineffective for severe CIP. At the same time, this case indicates that inflammatory factors, especially tumor necrosis factor (TNF-α), may be prospective in predicting the efficacy of infliximab in the treatment of steroid-refractory CIP.

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Section: Discussionmentioning

confidence: 99%

Infliximab in the treatment of tislelizumab-induced steroid-refractory immune checkpoint inhibitor-related pneumonia: case report and literature review

Chen¹,

He²

2022

Transl Cancer Res TCR

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“…If symptoms and laboratory findings in ICI myocarditis do not regress upon high-dose glucocorticoids, other immunosuppressant agents [e.g. mycophenolate mofetil, methotrexate, calcineurin inhibitors, intravenous immunoglobulin (IVIG), anti-thymocyte globulin, rituximab and infliximab] may be considered for treatment of ICIs cardiotoxicity, but data are still controversial ( 201 , 259 , 260 ).…”

Section: Potential Therapies and Prevention Of Iraesmentioning

confidence: 99%

Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events

et al. 2022

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Immune checkpoint inhibitors (ICIs) block inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1) and enhance antitumor T-cell activity. ICIs provide clinical benefits in a percentage of patients with advanced cancers, but they are usually associated with a remarkable spectrum of immune-related adverse events (irAEs) (e.g., rash, colitis, hepatitis, pneumonitis, endocrine, cardiac and musculoskeletal dysfunctions). Particularly patients on combination therapy (e.g., anti-CTLA-4 plus anti-PD-1/PD-L1) experience some form of irAEs. Different mechanisms have been postulated to explain these adverse events. Host factors such as genotype, gut microbiome and pre-existing autoimmune disorders may affect the risk of adverse events. Fatal ICI-related irAEs are due to myocarditis, colitis or pneumonitis. irAEs usually occur within the first months after ICI initiation but can develop as early as after the first dose to years after ICI initiation. Most irAEs resolve pharmacologically, but some appear to be persistent. Glucocorticoids represent the mainstay of management of irAEs, but other immunosuppressive drugs can be used to mitigate refractory irAEs. In the absence of specific trials, several guidelines, based on data from retrospective studies and expert consensus, have been published to guide the management of ICI-related irAEs.

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“…Since the New England Journal of Medicine first published the use of infliximab for fulminant myocarditis after immune checkpoint blockade in 2016, results from 18 patients using TNF-a antibodies for ICI-induced myocarditis have been reported (Tables 1 and 2) (71,(77)(78)(79)(80)(81)(82)(83)(84)(85)(86). The average age of these patients was 68 years; 9 of them were male.…”

Section: Tnf-a Antagonists For Ici-induced Myocarditismentioning

confidence: 99%

TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis

Liu

Fang

et al. 2022

Front. Immunol.

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With anti-PD-1 antibodies serving as a representative drug, immune checkpoint inhibitors (ICIs) have become the main drugs used to treat many advanced malignant tumors. However, immune-related adverse events (irAEs), which might involve multiple organ disorders, should not be ignored. ICI-induced myocarditis is an uncommon but life-threatening irAE. Glucocorticoids are the first choice of treatment for patients with ICI-induced myocarditis, but high proportions of steroid-refractory and steroid-resistant cases persist. According to present guidelines, tumor necrosis factor alpha (TNF-α) inhibitors are recommended for patients who fail to respond to steroid therapy and suffer from severe cardiac toxicity, although evidence-based studies are lacking. On the other hand, TNF-α inhibitors are contraindicated in patients with moderate-to-severe heart failure. This review summarizes real-world data from TNF-α inhibitors and other biologic agents for ICI-induced myocarditis to provide more evidence of the efficacy and safety of TNF-α inhibitors and other biologic agents.

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Treatment of corticosteroid refractory immune checkpoint inhibitor myocarditis with Infliximab: a case series

Cited by 22 publications

References 32 publications

Infliximab in the treatment of tislelizumab-induced steroid-refractory immune checkpoint inhibitor-related pneumonia: case report and literature review

Infliximab in the treatment of tislelizumab-induced steroid-refractory immune checkpoint inhibitor-related pneumonia: case report and literature review

Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events

TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis

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