Cardiac Toxicity After High-Dose Melphlan and Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

High-dose melphalan (HDM), 200 mg/m2, is the standard regimen for autologous hematopoietic stem cell transplant (auto-HCT) for multiple myeloma (MM). Although HDM-induced cardiotoxicity is reported, its incidence is not well known. In this retrospective analysis we evaluated the incidence of cardiotoxicity and its impact on outcome in patients undergoing auto-HCT for MM.

Three-hundred and sixty-nine consecutive patients who received melphalan 200 mg/m2 for auto-HCT ASCT between January 2006 and December 2009 were included in these analyses. Cardiac toxicity was defined as any cardiac adverse event reported from the day of administration of melphalan to day+ 30 after auto-HCT.

Patient characteristics are summarized in Table 1. Median age at auto-HCT was 59 years (32–78 years). Median time from diagnosis to auto-HCT was 8.0 months (1.8–266.3). Patients undergoing auto-HCT had a left ventricular ejection fraction (LVEF) of >40%, and no symptomatic cardiac disease. Thirty-five patients had concurrent or AL amyloidosis, and 43 patients had a prior history of cardiac disease. By day +30 after auto-HCT, 34 patients (9.2%) developed one or more adverse cardiac adverse events (AE). Twenty-seven patients experienced a single cardiac AE: atrial fibrillation (a fib): 16, congestive heart failure (CHF): 3, supraventricular tachycardia (SVT): 3, ischemic chest pain: 2, ventricular bigeminy: 1, diastolic dysfunction: 1 and sudden cardiac death in a patient with AL amyloidosis: 1. Seven patients had a combination of 2 or more cardiac adverse events: CHF + a fib: 4, ischemic chest pain + QT prolongation: 1, ischemic chest pain + left bundle branch block (LBBB): 1, ischemic chest pain + premature ventricular contractions (PVCs): 1. Overall, supraventricular arrhythmias were responsible for cardiac AE in 6.2% (23/369) of the patients. Twenty-eight patients (82%) fully recovered from the cardiac AE. Four patients required long term pharmacologic treatment of a fib, and one patient with a fib developed a cerebellar infarct without residual neurologic deficits. Patients with cardiac AE were older (median age: 62 vs. 59, p=0.014) and had a prior history of cardiac disease (17/34 vs. 20/335, p=0.0001) compared to patients without cardiac AE. Gender, concurrent AL amyloidosis, interval between diagnosis and auto-HCT, or transplant before or after the year 2000 were not associated with cardiac AE. Median overall follow up was 28 months (1–369). 100-day non-relapse mortality (NRM) was 3% (1/34) vs. 0% (0/335) in patients with or without cardiac AEs (p=0.09). Kaplan-Meier estimates of 3-year OS were 70% vs. 84% in patients with or without cardiac AE (p=0.084).

HDM and auto-HCT was associated with cardiac AEs in 9% of patients. A fib and CHF were the most common cardiac AEs, but >80% fully recovered without long-term sequelae. Patients with cardiac AE were relatively older and had a prior history of cardiac disease. There was no significant difference in NRM or OS in patients with or without melphalan-associated cardiac AEs.

<PR, includes Stable Disease, No Response, PD, Minimal Response; >=VGPR: includes Complete Remission (CR);, Very Good Partial Response and Partial Remission (VGPR), PR: Partial remission. RBBB (Right bundle branch block).

No relevant conflicts of interest to declare.