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16-11-2011 | Immunology | Article

Leukemia risk higher than expected in patients taking mitoxantrone for MS


Free abstract

MedWire News: Researchers find a high incidence of leukemia in patients receiving mitoxantrone (MTX) treatment for multiple sclerosis (MS), raising concerns over how long-term drug safety is monitored.

"An early retrospective study of MTX in MS had revealed a low incidence of therapy-related acute myelocytic leukemia (AML). Subsequent case and series reports have indicated that the incidence may be considerably higher," write Vittorio Martinelli (San Raffaele Scientific Institute, Milan, Italy) and co-authors, who attempted to "resolve" the issue with the present research.

The study, published in the journal Neurology, involved a sample of 3220 patients (63% women, mean age 44.2 years) from 40 Italian MS centers who had been treated with at least one infusion of MTX.

The patients were followed up for an average of 49 months, over which the team saw 30 cases of AML emerge. The median interval between the start of MTX treatment and AML diagnosis was 33.3 months.

The team reported a 0.93% incidence of AML, which translates to a global risk of one case in every 107 MTX-treated MS patients.

The mean cumulative dose of MTX was significantly higher in the patients with AML compared with the rest of the study cohort (78 vs 65 mg/m2), which the researchers say "suggest[s] a relationship between cumulative dose and the development of AML."

The incidence of AML reported here is described as "high" by Martinelli and team, after they compared the rate with an estimated 1:1000 rate of AML incidence in the Italian general population aged under 64 years.

"This finding contrasts with the absence of treatment-related leukemia in the early studies that supported the regulatory approval of MTX for this indication," say Martinelli et al. But they suggest that these early research findings may have been the result of small group sizes and short durations of experiments, which were designed for establishing efficacy rather than detecting adverse events.

They call for close monitoring of "the estimated tens of thousands of patients exposed to MTX over the past 6 years."

The study authors stress: "Early detection of hematologic abnormalities related to an incipient acute leukemia is crucial to preventing dramatic and fatal evolution of the disease. Suspected leukemia should be managed as a medical emergency."

They say the fact that it has taken 10 additional years of postmarketing surveillance to appreciate this risk should serve as a "warning for emerging therapies," and that, in the future, clinical practitioners should take responsibility for "active long-term surveillance in the real-world setting."

By Chloe McIvor

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