Treatment of multiple sclerosis (MS) patients with rituximab does not increase breast cancer risk in women, and is not associated with a higher risk for malignant cancer of any type in men or women, when compared to Gilenya (fingolimod) or Tysabri (natalizumab), according to a nationwide study in Sweden.
The study, “Cancer risk among Swedish multiple sclerosis patients: a nationwide cohort study comparing rituximab, fingolimod and natalizumab,” was presented at the 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place Oct. 10-12, in Berlin, Germany. The presenter was Karolinska Institutet, Stockholm, Sweden.
Increased cancer risk is a current long-term concern of using disease-modifying therapies (DMTs) able to exert greater effects on the immune system. This is supported by data from the ORATORIO Phase 3 trial (NCT01194570) in primary progressive MS patients, showing that treatment with the DMT Ocrevus (ocrelizumab, marketed by Genentech) was associated with an increased incidence of breast cancer.
Despite this information, long-term follow-up data on cancer risk in large, real-world groups of MS patients on novel DMTs are still scarce.
Aiming to address this gap, a team from the Karolinska Institutet, Sweden, assessed breast cancer risk among female MS patients treated with rituximab. The team also compared the risk of all types of malignant cancer in MS patients treated with different therapies, namely rituximab, Novartis’ Gilenya, and Biogen’s Tysabri.
Of note, rituximab — developed by Genentech and Biogen — has been used off-label, or outside the approved indications, in MS patients. The drug targets a protein called CD20 in immune B-cells, causing their depletion. Rituximab is approved by the U.S. Food and Drug Administration for the treatment of lymphoma, rheumatoid arthritis, ANCA vasculitis, and the rare skin disorder pemphigus vulgaris, and is sold under the brand name Rituxan.
The study was based on data from the Swedish MS register, linked to national healthcare and census registers, and included patients treated between 2011 and 2016.
Results revealed one case of malignant breast cancer in women with MS, among 2,274 rituximab treatment starts.
According to the team, this corresponds to an incidence rate of 2.32 cancers per 10,000 person-years (a measure that sums actual follow-up duration per patient), which is comparable to, or possibly lower than, the rate of the general female population (12.07 cancers per 10,000 person-years). And it is even lower than the rate reported in the ORATORIO trial with Ocrevus (26.1 cancers per 10,000 person-years).
The incidence rate of malignant breast cancer was 2.92 per 10,000 person-years in women taking Gilenya and 2.19 in those taking Tysabri.
As for the total group of patients (men and women) and regarding any type of malignant cancer, the data showed a total of 3,236 rituximab therapy starts, and 15 cancers of any type. The incidence rate was 24 cancers per 10,000 person-years.
In the other groups, the incidence rate of any type of malignant cancer was 46.28 per 10,000 person-years in those taking Gilenya, 23.09 in those taking Tysabri, and 29.62 in the general population.
Overall, “for malignant cancer of any type, we found no increased risk for RTX [rituximab], compared to FGL [Gilenya] and NTZ [Natalizumab],” Alping said in the presentation.
The “overall cancer risk and risk of breast cancer might not be major concerns short-term when treating MS patient with [rituxumab] relative to other DMTs,” Alping concluded.
Nonetheless, the team is cautious and emphasizes that “more detailed analyses are necessary.”
Of note, one of the study’s authors received research grants from pharmaceutical companies, including Novartis and Biogen.