Risks of heart problems after mitoxantrone

Low-risk of cardiotoxicity from mitoxantrone in MSers. #MSBlog #MSResearch

"This study on cardiac dysfunction comes hot on the heels on my post on mitoxantrone being one of the DMTs on the essential MS DMT list for healthcare settings in which high-cost licensed DMTs are not available. This article is interesting in relation to two issue; firstly, how much mitoxantrone was used in Germany and secondly how infrequent gross cardiac toxicity occurs in MSers treated with mitoxantrone. The figure of no cases of congestive cardiac failure out of 639 treated patient and only 26 or 4.1% with mild cardiac involvement is compatible with other publications on this topic. I suspect the incidence of cardiotoxicity in MS is low as MSers are relatively young and infrequently have other co-morbid cardiac pathologies. In addition, it is rare for MSers to have received other cardiotoxic drugs prior to receiving mitoxantrone; this is not the same in other settings in which mitoxantrone is used, particularly in the field of oncology. Please note that cardiotoxicity is dose related and hence nobody with MS should receive more than 140mg/m-squared and they should all have their cardiac function monitored during the period of treatment so the drug can be stopped to prevent irreversible cardiac damage."


Fleischer et al. Cardiotoxicity of mitoxantrone treatment in a german cohort of 639 multiple sclerosis patients. J Clin Neurol. 2014 Oct;10(4):289-95.

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). 

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