Early lymphocyte recovery predicts cardiovascular events and mortality in immune checkpoint inhibitor-associated myocarditis: a retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitor-associated myocarditis is an uncommon but potentially fatal cardiovascular toxicity of cancer immunotherapy. Early risk stratification remains challenging, and readily available biomarkers are needed. We investigated whether early changes in absolute lymphocyte count (ALC) were associated with major adverse cardiovascular events (MACE) and overall survival in patients with immune checkpoint inhibitor-associated myocarditis. METHODS: This retrospective cohort study included 60 patients diagnosed with immune checkpoint inhibitor-associated myocarditis. Absolute lymphocyte count was measured serially during the first 9 days after corticosteroid initiation. A Day-9 landmark design was used to assess associations between lymphocyte dynamics and subsequent outcomes. The primary endpoint was 60-day major adverse cardiovascular events, and the secondary endpoint was 1-year overall survival. Cox regression, Kaplan-Meier analysis, receiver operating characteristic analysis, and restricted cubic spline modeling were performed. RESULTS: Among 60 patients, 28 (46.7%) developed MACE in 60 days. Patients who developed MACE had persistently lower ALC levels and impaired early lymphocyte recovery. Day-9 ALC demonstrated good discrimination for MACE (AUC = 0.816) and remained independently associated with lower risk after multivariable adjustment (HR 0.33, 95% CI 0.14-0.81; p = 0.016). The association between Day-9 ALC and MACE risk was nonlinear, with lower estimated risk at higher ALC levels. Faster lymphocyte recovery was also independently associated with lower MACE risk (HR 0.07 per 0.1 × 109/L/day, 95% CI 0.01-0.44; p = 0.004). Both lower Day-9 ALC and impaired recovery were associated with worse 1-year overall survival. CONCLUSIONS: In patients with immune checkpoint inhibitor-associated myocarditis, lower Day-9 absolute lymphocyte count and slower early lymphocyte recovery were associated with adverse cardiovascular events and mortality. Serial absolute lymphocyte count assessment may provide a simple and clinically accessible approach for early risk stratification, although external validation is needed.