Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis

Abstract

BackgroundMyocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST.MethodsThis case–control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca’s criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not.ResultsA total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005).ConclusionThe need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events

“…Moreover, infliximab use was associated with increased risk of death from cardiovascular causes (odds ratio (OR) 12.0; 95% CI 2.1 to 67.1; p=0.005). 324 Thromboembolic events Attribution of thromboembolic events to ICI therapy may be difficult, since these events may occur as a result of cancer. 325 326 Venous thromboembolism (VTE), in fact, is one of the most common causes of mortality in patients with cancer.…”

Cardiotoxicities of novel cancer immunotherapies

“…2 6 9 However, infliximab should be avoided due to reports of increased cardiovascular mortality, particularly with moderate-to-severe HF. 23 ICI-associated myocarditis can progress to cardiogenic shock, life-threatening arrhythmias and death. Inpatient monitoring of grade 3 or 4 ICI-associated myocarditis patients is needed to monitor for decompensation and arrhythmias requiring temporary or permanent pacemaker placement.…”

A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors

“…Cardiac AE encompasses a diverse set of disorders in the heart including myocarditis, pericarditis, arterial vascular disease, venous thromboembolism, pulmonary hypertension, arrhythmias, and heart failure. Further complicating the differential diagnosis and reporting, is the fact that more than one immune-related adverse event may occur with another [ 7 ]. Which clinical features predispose cancer patients to immune-associated cardiac AE remains poorly understood.…”