Immunotherapy continuation after mild immune checkpoint inhibitor-associated myocarditis in lung cancer: a retrospective cohort study

Immune checkpoint inhibitor-associated myocarditis (ICI-M) is one of the most severe manifestations among immune-related adverse events (irAEs). However, evidence regarding the safety and efficacy of continuing immune checkpoint inhibitors (ICIs) after mild ICI-M remains limited. This retrospective cohort study included 357 patients diagnosed with grade 1-2 ICI-M between June 2016 and August 2024, according to the International Cardio-Oncology Society (IC-OS)-defined CTCAE grading system. Patients were stratified into permanent discontinuation and continuation groups. Safety outcomes included the incidence of recurrent ICI-M, new irAEs, and major adverse cardiovascular events (MACE). Efficacy outcomes included overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to reduce selection bias. Over a median follow-up of 18 months, the recurrence rate of ICI-M was 8.8% among patients who continued ICI treatment. The Common Terminology Criteria for Adverse Events (CTCAE) grade, peak cardiac troponin I (cTnI) levels, and peak creatine kinase-myocardial band (CK-MB) levels were comparable between the initial and recurrent episodes. New irAEs occurred in 13.3% of patients. Patients with recurrent ICI-M or new irAEs had an earlier onset of initial ICI-M and higher peak CK-MB levels during the initial episode. ICI continuation was not associated with increased MACE risk (multivariable subdistribution hazard ratio: 1.29; 95% CI: 0.49–3.42; P = 0.600) but was independently associated with longer OS (multivariable HR: 0.48; 95% CI: 0.35–0.64; P < 0.001) and PFS (multivariable HR: 0.51; 95% CI: 0.39–0.67; P < 0.001). These benefits remained consistent after PSM and IPTW. In patients with CTCAE grade 1-2 ICI-M, continuation of ICIs was associated with relatively low recurrence rates, no excess risk of MACE, and longer OS and PFS. Given the limitations of the retrospective design, large-scale prospective studies are required to validate these findings.