A prospective study to detect ICIs’ associated Myocarditis, among patients treated for lung cancer

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) are widely used in lung cancer management. Myocarditis is a potentially severe but rare adverse event (AE) associated with ICIs. Our aim was to prospectively evaluate the incidence of subclinical myocarditis through systematic screening among patients receiving ICIs for lung cancer.

Methods: We included prospectively every patient receiving a first administration of ICIs for lung cancer, between May and November 2020 and performed systematically echocardiography, ECG, troponin and natriuretic peptide dosages before ICIs’ first administration, and troponin, natriuretic peptide dosages and ECG before each infusion. In case of elevation of troponin or ECG modification we performed echocardiography, magnetic resonance imaging and coronoragraphy. The primary outcome was myocarditis onset during a 6-month follow-up. Secondary outcomes were other cardiovascular events, overall and progression-free survival.

Results: Among 143 patients treated with ICIs for lung cancer, 100 received their 1st infusion of ICIs (mean age 64 years; 51 men, 66 adenocarcinoma). During a mean follow-up of 6 months, 3 cases of myocarditis occurred (2 definite and 1 possible), 2 under atezolizumab, 1 under pembrolizumab, 0 under double ICIs. They were subclinical, with a mean interval duration between 1st ICIs administration and myocarditis onset of 144+/-3 days.

Conclusion: Among patients treated with ICIs for lung cancer, subclinical myocarditis occurred more frequently and later than previously described. Practitioners should pay more attention to this probably underestimated AE especially in light of the increase of ICI’s prescription.