Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS

Background: Mitoxantrone (MITO) is associated with dose-related cardiotoxicity when administered concomitantly with other cytotoxic agents with or without radiotherapy for leukemia and solid tumors. Objective: To review observed cardiotoxicity of single-agent MITO therapy for MS. Methods: Records of 1,378 patients from three clinical trials of MITO treatment for MS were reviewed for signs and symptoms of cardiac dysfunction and left ventricular ejection fraction (LVEF) results. Duration of follow-up was a median of 29 months (4,084 patient-years). Results: No patients experienced congestive heart failure (CHF) before treatment. Cumulative MITO doses ranged from 2 to 183 mg/m(2) (mean 60.5 mg/m(2), median 62.5 mg/m(2)), and 141 patients received >100 mg/m(2). Two of 1,378 patients experienced CHIP after initiating MITO therapy. Of 1,378 patients, 779 completed baseline and scheduled follow-up LVEF testing. Baseline LVEF was >50% in all 779 patients. Seventeen of 779 patients had asymptomatic LVEF of <50% (incidence proportion = 2.18%, 95% CI = 1.28 to 3.47%). Although the incidence of asymptomatic LVEF of <50% was not significantly related to monthly versus 3-monthly therapy, duration of therapy, age, or gender, asymptomatic LVEF of <50% trended higher with a cumulative dose of ≥100 mg/m(2) (5.0%) than with <100 mg/m(2) (1.8%) (P = 0.06). Conclusions: The observed incidence of CHIP in patients with MS who received a mean cumulative dose of 60.5 mg/m(2) MITO was <0.20%. Continued monitoring of patients with MS who are receiving MITO is needed to determine whether the incidence of CHIP increases with higher cumulative MITO doses and prolonged follow-up.