A Prospective Study to Detect Immune Checkpoint Inhibitors Associated With Myocarditis Among Patients Treated for Lung Cancer

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) are widely used in lung cancer management. However, myocarditis, which is a rare, yet potentially severe adverse-related event associated with ICIs, could be under-reported.ObjectivesThis study is aimed to prospectively evaluate the cumulative incidence rate of myocarditis, through systematic screening, among patients receiving ICIs for lung cancer.MethodsAll patients who received the first administration of ICIs for non-small cell (NSCLC) and small cell lung cancer (SCLC), between May and November 2020, in the pulmonary department of Bordeaux University Hospital, were included. Echocardiography (ECG), troponin-I, and natriuretic peptide dosages before ICIs' first administration and before each infusion were recorded. ECG and magnetic resonance imaging (MRI) were done additionally, in case of at least three times increase in troponin levels, ECG modifications, and the onset of cardiovascular symptoms. Second, if possible, coronarography than endomyocardial biopsy was assessed. The primary outcome was defined as ICIs related to myocarditis onset, while secondary outcomes included other cardiovascular events, disease-free, and overall survival.ResultsDuring the period of interest, 99 patients received their first infusion of ICIs for lung cancer (mean age 64 ± 9 years; 52 men, 67% with adenocarcinoma). Three cases of myocarditis without major adverse cardiac events (MACEs) occurred (two definite and one possible), and the mean duration between the first ICIs' administration and myocarditis onset was 144 ± 3 days. Median disease-free survival and overall survival were 169 [102; 233] days and 209 [147; 249] days, respectively.ConclusionIn our study, systematic screening of myocarditis associated with ICIs leads to a more frequent incidence and a later onset than previously reported. None of them were severe. Additional prospective evidence is needed before we could adopt routine cardiac screening in unselected patients starting ICIs; however, these data shed new light on the risk of myocarditis associated with ICIs administration.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

“…Systematic screening was also performed in a prospective, single-center study by Faubry et al which included 99 patients [55]. The main objective was to determine the incidence of myocarditis and other CV irAEs in ICI-treated patients with stage IIIB-IV lung cancer.…”

Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta‐Analysis of Observational Studies and Randomized Controlled Trials

“…In the OSs, our results show that ICI use was not associated with increased risk of myocarditis ( P =0.09) or pericardial disease ( P =0.19, Figure 6 , 14 , 17 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ). However, the use of combination ICIs was associated with higher risk of myocarditis (OR, 3.07 [95% CI, =1.28–7.39], P <0.02) but not pericardial disease (OR, 4.13 [95% CI, 0.19–89.86], P <0.67) compared with single ICI therapy in OSs.…”

“… Forest plot of included OSs, separated based on therapy comparisons for myocarditis 14 , 17 , 53 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ( A ) and pericardial disease 17 , 53 , 54 , 55 , 56 ( B ). The squares and horizontal lines correspond to the study‐specific ORs and 95% CIs.…”

Underreporting of Major Cardiac Adverse Events With Immune Checkpoint Inhibitors in Clinical Trials: Importance of Postmarketing Pharmacovigilance Surveys

“…Notwithstanding, we were taken aback by the very low incidence of ICI-related MACE in this pooled analysis of trials (0.6% of patients treated), with an incidence of myocarditis as low as 0.26%, whereas myocarditis may occur in more than 1% of patients 3 with a recent report of a 3% incidence through a prospective study in patients with lung cancer. 4 Additionally, a recent retrospective study reported an incidence of 10.3% of nonmyocarditis MACEs (acute coronary syndrome, heart failure, stroke, and transient ischemic attack) through a median follow-up of 13 months. 5 This underestimation of ICI-related MACE found in the NCI trials database may stem from numerous facts.…”