Mitoxantrone for Severe MS Linked To Increased Risk of Colon Cancer and Leukemia Interview with:

PD Dr. Mathias Buttmann Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic University of Wuerzburg Wuerzburg, German

Dr. Mathias Buttmann

PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany What is the background for this study? What are the main findings?

Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated  multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.

Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer. What should clinicians and patients take away from your report?

Dr. Buttmann: In addition to a known risk of acute myeloid leukemia, mitoxantrone may moderately increase the risk of colorectal cancer in multiple sclerosis patients, while the overall incidence of malignancies appears to be only mildly increased as compared to the general population. These findings await independent confirmation before additional safety measures after mitoxantrone treatment, such as colonoscopies, might become advisable. Mitoxantrone remains a beneficial drug in carefully selected patients with progressive disabling disease, for whom no other approved treatment is available. What recommendations do you have for future research as a result of this study?

Dr. Buttmann: I hope that other clinical researchers will soon start to investigate the incidence of colorectal cancer in their mitoxantrone-treated patients to confirm or hopefully refute our finding which might have occurred by chance. Is there anything else you would like to add?

Dr. Buttmann
: I would like to thank our patients and their treating physiciancs for their tremendous support of this study, allowing a follow-up quote that is unusual for this type of retrospective study. Thank you for your contribution to the community.


Buttmann, L. Seuffert, U. Mader, K. V. Toyka.
Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study.
Neurology, 2016; DOI:10.1212/WNL.0000000000002745

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Last Updated on May 13, 2016 by Marie Benz MD FAAD