Cancer Increase Seen in Modern Era of MS Drugs

Nancy A. Melville

February 28, 2020

WEST PALM BEACH, Florida — Cancer incidence rates among patients with multiple sclerosis (MS) treated after the advent of immune therapies show an increase compared with prior generations, according to a large study of Norwegian patients with MS.

"We detected a similar cancer risk among MS patients compared to the general Norwegian population before 1996, [however], MS patients had an increased risk of cancer compared to the general population after 1996," first author Nina Grytten, PhD, of the Department of Neurology, Norwegian Multiple Sclerosis Centre, Bergen, told Medscape Medical News.

"This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients."

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented Jeffrey A. Cohen, MD, president of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

"Something that's already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we're talking about a life-long therapy for most people," Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research, Cleveland Clinic, Ohio, told Medscape Medical News.

"With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it's something we should pay attention to," he said.

The study was presented here on February 27 at the fifth annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020.

In previous research, Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of incidence rates according to sex and period of diagnosis.

For the study, they identified a total of 6638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

Patients were then matched with 36,957 Norwegian citizens without MS in a 5:1 ratio based on age, gender, and county.

The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data.

Participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, cancer diagnosis rates were similar between participants with MS (774; 11.2%) and without MS (4; 10.6%).

And in looking at cancer incidence rate ratios (IRRs) of those with MS compared to controls between 1953 and 1995, the rate was similar (IRR, 1.05; 95% CI, 0.97 - 1.14).

However, after 1995, the rate increased, with a higher cancer incidence among patients with versus without MS (IRR, 1.40; 95% CI, 1.30 - 1.51).

Additionally, cancer rates were higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28 - 2.40), meninges (IRR, 2.28; 95% CI, 1.47 - 3.53), urinary organs (IRR, 2.06; 95% CI, 1.52 - 2.79), digestive system (IRR, 1.47; 95% CI, 1.20 - 1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06 - 2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55 - 2.07).

Grytten noted, however, that the study cannot rule out various other possible causes for the differences.

For instance, "cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of DMTs," she noted. "Those are possibly caused by smoking, which is a habit more common among MS patients in Norway."

Furthermore, she added, "increased cancer in the central nervous system in MS could possibly be explained by frequent use of MRI and the ability to detect central nervous system cancer at early stages."

"There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities."

However, the finding that increased cancers were also observed after 1996 in the other organs of patients with MS does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer, and "other immunosuppressant drugs, including the MS drug fingolimod, are believed possibly to be linked to an increased cancer risk, although evidence has not yet been established," Grytten said.

"The increased risk of cancer associated with MS was detected in the era of DMT of MS, and this association suggests that DMTs might possibly increase cancer risk."

In general, "clinicians should be aware of comorbidity in MS," Grytten said. "More data are needed on the long-time effects of immunomodulatory treatment."

Cohen added that — in addition to mitoxantrone — azathioprine and cyclophosphamide have shown risk; however, "clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring."

"Nevertheless, this study suggests that in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed-up," he said.

Grytten has reported no relevant financial relationships. Cohen has reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an editor of the Multiple Sclerosis Journal.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020. Abstract P126. Presented February 27, 2020.

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