NT-proBNP serves as a prognostic marker for adverse outcomes in severe immune checkpoint inhibitor-associated myocarditis

Background Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but carry risks of rare, life-threatening immune-related adverse events, particularly myocarditis. Prognostic biomarkers and optimal management strategies for severe ICI-associated myocarditis remain poorly defined. Methods This single-center retrospective cohort study analyzed 71 patients diagnosed with ICI-associated myocarditis among 7,157 ICI-treated individuals at a tertiary center (August 2018–August 2024). Myocarditis severity was graded per American Society of Clinical Oncology (ASCO) guidelines. Cardiac biomarkers, including NT-proBNP and troponin T, were assessed. Binary logistic regression identified predictors of mortality. Treatment protocols and immunotherapy rechallenge outcomes were evaluated. Results Severe myocarditis (Grades 3–4) occurred in 33 patients (46.5%), with an overall mortality rate of 54.5% in this subgroup (18/33). NT-proBNP levels were significantly elevated in fatal cases versus survivors (median: 13,804 vs. 4,050 pg/mL; P < 0.001) and independently predicted mortality risk (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.2–21.9; P = 0.023). A multimodal regimen combining plasmapheresis with high-dose corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil was associated with improved survival. Among nine patients rechallenged with immunotherapy, seven (77.8%) tolerated subsequent cycles without recurrent immune toxicity, while two with prior Grade 2 myocarditis experienced symptom recurrence. Discussion Elevated NT-proBNP emerges as a critical prognostic marker for risk stratification in severe ICI-associated myocarditis. Immunotherapy rechallenge appears feasible in select patients but warrants caution in those with prior moderate-grade myocarditis. These findings advocate for biomarker-guided escalation of therapies and shared decision-making frameworks to balance oncologic efficacy with cardiovascular safety.