WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“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 ACTRIMS president, Jeffrey A. Cohen, MD.
“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,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“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.
In previous research, Dr. 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 cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to 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. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally 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).
Dr. 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 disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS 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 observed after 1996 in other organs in MS patients as well 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 to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “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.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.