J Clin Neurol.  2014 Oct;10(4):289-295. 10.3988/jcn.2014.10.4.289.

Cardiotoxicity of Mitoxantrone Treatment in a German Cohort of 639 Multiple Sclerosis Patients

• Fleischer
• Salmen A
• Kollar S
• Weyer V
• Siffrin V
• Chan A
• Zipp F
• Luessi F

• KMID: 2287507
• DOI: http://doi.org/10.3988/jcn.2014.10.4.289

Abstract

BACKGROUND AND PURPOSE
The aim of this study was to elucidate the role of therapy-related cardiotoxicity in multiple sclerosis (MS) patients treated with mitoxantrone and to identify potential predictors for individual risk assessment.
METHODS
Within a multicenter retrospective cohort design, cardiac side effects attributed to mitoxantrone were analyzed in 639 MS patients at 2 MS centers in Germany. Demographic, disease, treatment, and follow-up data were collected from hospital records. Patients regularly received cardiac monitoring during the treatment phase.
RESULTS
None of the patients developed symptomatic congestive heart failure. However, the frequency of patients experiencing cardiac dysfunction of milder forms after mitoxantrone therapy was 4.1% (26 patients) among all patients. Analyses of the risk for cardiotoxicity revealed that cumulative dose exposure was the only statistically relevant risk factor associated with cardiac dysfunction.
CONCLUSIONS
The number of patients developing subclinical cardiac dysfunction below the maximum recommended cumulative dose is higher than was initially assumed. Interestingly, a subgroup of patients was identified who experienced cardiac dysfunction shortly after initiation of mitoxantrone and who received a low cumulative dose. Therefore, each administration of mitoxantrone should include monitoring of cardiac function to enhance the treatment safety for patients and to allow for early detection of any side effects, especially in potential high-risk subgroups (as determined genetically).

Keyword

multiple sclerosis; mitoxantrone; cardiotoxicity; dose dependency

MeSH Terms

Cohort Studies*
Follow-Up Studies
Germany
Heart Failure
Hospital Records
Humans
Mitoxantrone*
Multiple Sclerosis*
Retrospective Studies
Risk Assessment
Risk Factors
Mitoxantrone

Figure

• 

  Fig. 1 Analyses of potential relationships between the occurrence of cardiac events and patient characteristics. The cumulative dose was significantly higher in the patients group with cardiac events. No significant difference was observed between gender, age at initial diagnosis, disability before MX treatment or disease course, and the incidence of cardiac events. Data are mean and SEM values; *p<0.05. BSA: body surface area, EDSS: Expanded Disability Status Scale, MX: mitoxantrone, PPMS: primary progressive multiple sclerosis, RRMS: relapsing-remitting multiple sclerosis, SPMS: secondary progressive multiple sclerosis.

• 

  Fig. 2 Patients with cardiac events. A: Event-free curves (Kaplan-Meier curves) indicating the proportion of patients without cardiac dysfunction over the observation period (in years). B: The incidence of cardiac events by cumulative dose shown as the percentage of patients.

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