Factors Associated With Immune Checkpoint Inhibitor–Related Myocarditis

Zamami, Yoshito; Niimura, Takahiro; Okada, Naoto; Koyama, Toshihiro; Fukushima, Keijo; Izawa‐Ishizawa, Yuki; Ishizawa, Keisuke

doi:10.1001/jamaoncol.2019.3113

Cited by 95 publications

(77 citation statements)

References 6 publications

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“…Furthermore, the research using the SRS database focuses on myasthenia gravis, 14 and myocarditis. 13 Using the FAERS database, Ji et al 10 comprehensively evaluated AE profiles, including irAEs using Standardized MedDRA Queries 20 that consist of PTs grouped according to the level that relates to a defined medical condition. Based on previous reports, 3,6,[9][10][11]13,14,19,21 we categorized irAEs into the following 14 groups: adrenal insufficiency, colitis, eye disease, hematological disorder, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia gravis, myocarditis, nephritis/renal dysfunction, pneumonitis, rash, and type 1 diabetes mellitus and selected PTs for each category (Table 1).…”

Section: Target Drugs and Iraesmentioning

confidence: 99%

“…67 Several studies based on the FAERS database have reported ROR signals for myocarditis. 10,13 We conducted a time-to-onset analysis of the JADER data set and found that the median onset of myocarditis was 3 to 4 weeks follow- A wide range of renal dysfunction symptoms were often observed with the anti-PD-1 antibody. 3,9,10 Rash was a common dermatological AE induced by anti-PD-1 antibodies and the anti-CTLA-4 antibody, ipilimumab.…”

Section: Thyroid Dysfunction Following Treatment With Anti-pd-1 Anti-mentioning

confidence: 99%

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Analysis of immune‐related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database

Hasegawa

Ikesue

Nakao

et al. 2020

Pharmacoepidemiology and Drug

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The aim of our study was to characterize the clinical features of immunerelated adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database. Methods: The irAEs were defined using the preferred terms of the Medical Dictionary for Regulatory Activities. irAEs were categorized as follows: adrenal insufficiency, colitis, eye diseases, hematological disorder, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia gravis, myocarditis, nephritis/renal dysfunction, pneumonitis, rash, and type 1 diabetes mellitus. We used several indices such as reporting odds ratio (ROR) to assess disproportionality in pharmacovigilance data, time-to-onset analysis using Weibull shape parameters, and the association rule mining technique to evaluate possible risk factors between variables in the spontaneous reporting system database.

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Section: Target Drugs and Iraesmentioning

confidence: 99%

Section: Thyroid Dysfunction Following Treatment With Anti-pd-1 Anti-mentioning

confidence: 99%

Analysis of immune‐related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database

Hasegawa

Ikesue

Nakao

et al. 2020

Pharmacoepidemiology and Drug

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“…Immune checkpoint inhibitors (ICI), including combination therapies such as ipilimumab plus nivolumab, have shown remarkable efficacy across multiple tumor types (1)(2)(3)(4)(5) but are associated with immune-related adverse events (irAEs) including myocarditis (6)(7)(8)(9)(10). ICI-associated myocarditis is characterized by myocardial T cell and macrophage infiltration, significant electrocardiographic disturbances, with preliminary data suggesting a female predominance, clinically distinguishing it from other forms of myocarditis (7,11,12). ICI-associated myocarditis is also often fulminant and fatal, despite corticosteroid therapy.…”

Section: Introductionmentioning

confidence: 99%

A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor–Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention

et al. 2021

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Therapeutics, BioNTx, and Polaris. L.L. serves on advisory boards for Servier. S.C.W. and J.P.A. are inventors of a patent application submitted by The University of Texas MD Anderson Cancer Center related to a genetic mouse model of immune checkpoint blockade induced immune-related adverse events. S.C.W. is currently an employee of Spotlight Therapeutics. E.M.W has ownership interest in Pathogenesis, LLC. W.C.M. was supported by funding from the Niels Stensen Fellowship and the Netherlands Heart Institute. D.B.J serves on advisory boards for Array Biopharma, BMS, Merck, Novartis; research funding from BMS and Incyte. J.E.S serves on advisory boards for BMS. J.E.S, D.B.J and J.J.M are inventors of a patent application submitted by The Assistance Publique-Hopitaux de Paris related to abatacept for the treatment of immune-related adverse events associated with immune checkpoint inhibitors. Research.

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“…These irAEs affect various organs, such as the skin, endocrine glands, gastrointestinal tract, and liver, but only a few events are fatal because the majority of them can be controlled by adequate treatment 5 , 7 . Specifically, ICI-related interstitial lung disease (ICI-ILD) has a low incidence (1–5%) and a high severity or mortality rate, according to clinical trials (50–60%) 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study

Okada

Matsuoka

Sakurada

et al. 2020

Sci Rep

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Immune checkpoint inhibitors (ICIs) elicit antitumour effects by activating the host immunity and cause immune-related adverse events (irAes). ici-related interstitial lung disease (ici-iLD) is a fatal irAE that is difficult to treat; moreover, its incidence is relatively higher in patients with lung cancer. therefore, early ici-iLD detection and intervention are important for patient safety. However, a risk assessment method for ici-iLD has not been established and the prediction of ici-iLD occurrence is difficult. The aim of our study was to identify the risk factors associated with ICI-ILD. To this end, we retrospectively analysed 102 patients with lung cancer who first received ICI and completed the treatment between April 2016 and December 2019 at Tokushima University Hospital. Nineteen patients had all grades of ICI-ILD and 10 had grade ≥ 3 ICI-ILD. The 30-day mortality rate of patients with grade ≥ 3 ICI-ILD was the highest among all patients (P < 0.01). The multivariate logistic analysis indicated that the performance status ≥ 2 alone and both performance status ≥ 2 and ≥ 50 pack-year were independent risk factors of ICI-ILD of grade ≥ 3 and all grades, respectively. Overall, our study provides insights to predict ici-iLD occurrence. Immune checkpoint inhibitors (ICIs) are antibodies that inhibit programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), which are called immune checkpoint molecules. These molecules negatively regulate the host immunity; thus, the inhibition of these molecules activates the host immunity and exerts cross-organ antitumour effects 1. In the treatment of lung cancer, some clinical trials have revealed that the administration of ICI alone and in combination with cytotoxic anticancer agents resulted in better clinical outcomes than previous standard treatments; thus, the use of ICI significantly improved lung cancer treatment 2-4. However, the activation of the host immunity by ICI leads to characteristic adverse events, known as immune-related adverse events (irAEs), which exhibit profiles different from those caused by cytotoxic anticancer agents 5,6. Therefore, the management of irAEs is essential for an effective ICI treatment. These irAEs affect various organs, such as the skin, endocrine glands, gastrointestinal tract, and liver, but only a few events are fatal because the majority of them can be controlled by adequate treatment 5,7. Specifically, ICI-related interstitial lung disease (ICI-ILD) has a low incidence (1-5%) and a high severity or mortality rate, according to clinical trials (50-60%) 8,9. Patients with lung cancer are known to have relatively higher ICI-ILD rates than those with other cancers 10. A prospective study of patients with lung cancer reported that the incidence of ICI-ILD was 14.5%, which is higher than that in clinical trials 11. ICI-ILD has also been reported to affect the prognosis of patients with lung cancer 11,12 .

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Factors Associated With Immune Checkpoint Inhibitor–Related Myocarditis

Cited by 95 publications

References 6 publications

Analysis of immune‐related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database

Analysis of immune‐related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database

A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor–Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention

Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study

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