Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis

Hasson, Shira Peleg; Salwen, Benjamin; Sivan, Ayelet; Shamai, Sivan; Merimsky, Ofer; Raphael, Ari; Shmilovich, Haim; Moshkovits, Yonatan; Kapusta, Livia; Rozenbaum, Zach; Wolf, Ido; Laufer‐Perl, Michal

doi:10.1007/s00392-020-01648-3

Cited by 24 publications

(19 citation statements)

References 37 publications

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“…At present, the American Society of Clinical Oncology guideline recommends permanent cessation with grade 1 toxicity (abnormal cardiac biomarker testing including ECG), 26 while some centers have proposed a cautious reinitiation of ICI therapy with or without low dose steroids. 27 In our study, two patients with subclinical myocarditis (grade 1 toxicity) were re-introduced to immunotherapy following normalization of their cardiac parameters. In one case the troponin elevation returned, and ICI therapy was discontinued permanently.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis

Puzanov

Subramanian²,

Yatsynovich

et al. 2021

J Immunother Cancer

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BackgroundImmune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs.MethodsWe retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors.ResultsAmong patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes.ConclusionsRoutine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis

Puzanov

Subramanian²,

Yatsynovich

et al. 2021

J Immunother Cancer

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“…There is a paucity of data as to which patients, if any, can be rechallenged with ICI. 69 In cases in which ICI-associated myocarditis can be excluded, corticosteroids may be discontinued. In cases of highdose steroid therapy longer than 3 days, which is frequently associated with a suppression of the adrenal response, a reduction scheme should be considered.…”

Section: Treatment Considerationsmentioning

confidence: 99%

Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor–Associated Myocarditis

et al. 2021

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“…In patients undergoing cancer-related treatment, Haslbauer et al observed a parallel increase in native T1 and T2 values when CMR scans were performed early after treatment initiation [54], indicating underlying myocardial edema; on the other hand, cases that underwent a late CMR examination (more than 12 months post-treatment) were more likely to have increased native T1 and lower T2 values, indicating fibrosis and cardiac remodeling. Re-challenge with ICI is currently a debated topic, and it has been hypothesized that reintroduction in low-grade patients might be a feasible option, albeit better definition of the grading is needed [55]. Potentially, CMR imaging biomarkers, especially the prognostic relevant native T1, could serve as criteria for considering a patient eligible for re-challenge with ICI.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Magnetic Resonance Imaging in Immune Check-Point Inhibitor Myocarditis: A Systematic Review

Arcari¹,

Tini

Camastra³

et al. 2022

J. Imaging

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Immune checkpoint inhibitors (ICIs) are a family of anticancer drugs in which the immune response elicited against the tumor may involve other organs, including the heart. Cardiac magnetic resonance (CMR) imaging is increasingly used in the diagnostic work-up of myocardial inflammation; recently, several studies investigated the use of CMR in patients with ICI-myocarditis (ICI-M). The aim of the present systematic review is to summarize the available evidence on CMR findings in ICI-M. We searched electronic databases for relevant publications; after screening, six studies were selected, including 166 patients from five cohorts, and further 86 patients from a sub-analysis that were targeted for a tissue mapping assessment. CMR revealed mostly preserved left ventricular ejection fraction; edema prevalence ranged from 9% to 60%; late gadolinium enhancement (LGE) prevalence ranged from 23% to 83%. T1 and T2 mapping assessment were performed in 108 and 104 patients, respectively. When available, the comparison of CMR with endomyocardial biopsy revealed partial agreement between techniques and was higher for native T1 mapping amongst imaging biomarkers. The prognostic assessment was inconsistently assessed; CMR variables independently associated with the outcome included decreasing LVEF and increasing native T1. In conclusion, CMR findings in ICI-M include myocardial dysfunction, edema and fibrosis, though less evident than in more classic forms of myocarditis; native T1 mapping retained the higher concordance with EMB and significant prognostic value.

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Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis

Cited by 24 publications

References 37 publications

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis

Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor–Associated Myocarditis

Cardiac Magnetic Resonance Imaging in Immune Check-Point Inhibitor Myocarditis: A Systematic Review

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