Mitoxantrone Linked to Elevated Cancer Risk in Multiple Sclerosis Patients

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Mitoxantrone Linked to Elevated Cancer Risk in Multiple Sclerosis Patients
Mitoxantrone Linked to Elevated Cancer Risk in Multiple Sclerosis Patients

Patients with multiple sclerosis (MS) who are treated with mitoxantrone may have a greater risk of colon cancer and acute myeloid leukemia (AML), German researchers reported.

“Despite an increased risk of acute myeloid leukemia and colorectal cancer, the overall rate of cancer was low enough to justify still using this drug for people severely affected by MS if no better treatment is available,” study author Mathias Buttmann, MD, said in a press release.

Mitoxantrone is a cytotoxic anthracenedione used as a disease-modifying drug in secondary progressive, progressive relapsing and relapsing-remitting MS. Its use has previously been tied to AML, however its association with other malignancies is not known.

Dr Buttmann, of the University of Würzburg in Germany, and colleagues conducted a retrospective observational cohort study from 1994 to 2007 in patients treated with mitoxantrone to characterize the risk of malignancy. Data was obtained on death and confirmed malignancy and was compared to malignancy rates from the German national cancer registry.

The cohort included 677 patients with complete data available for 676 patients over an average follow-up of 8.7 years. Females made up 67.2% of the cohort with a mean age at initiation of mitoxantrone of 41 years.

Malignancy was confirmed in 5.5% (n=37) of the study patients. Diagnoses included colorectal cancer (n=7),AML (n=4), breast cancer (n=9), prostate cancer, lung cancer, glioblastoma multiforme, and pancreatic cancer (n=2 each). The 7 patients diagnosed with colon cancer were diagnosed at an advanced stage and 3 died secondary to the malignancy.

During follow-up, 8.1% (n=55) of participants had died, with 12 deaths attributed to malignancy.

The standardized incidence ratio of malignancy was 1.50 (95% CI: 1.05-2.08) and 2.98 (95% CI: 1.20-6.14) for colorectal cancer and 10.44 (95% CI: 3.39-24.36) for AML. A higher age at mitoxantrone initiation was identified as a potential risk factor for malignancy by Multivariate Cox regression analysis. However, neither treatment with other immunosuppressives or a higher cumulative mitoxantrone dose was found to be a risk factor.

The authors pointed out several limitations of the study, included a small cohort, a lack of autopsies performed on the deceased, and limited follow-up.

"In our cohort of mitoxantrone-treated patients with MS, we observed a previously undescribed 3-fold increased incidence of colorectal cancer and a 10-fold increased incidence of AML, while the overall rate of all malignancies was only mildly increased as compared to the general population," the authors wrote.

If the results are confirmed, screening colonoscopy may be indicated after treatment with mitoxantrone.

Reference

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

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