Background: Cyclophosphamide is still used in progressive forms of multiple sclerosis (MS) in view of its suggested efficacy and safety in the short term. No data exist on its long-term safety in MS, particularly on the risk of malignancy. Objective: The objective of this study was to evaluate cancer incidence in MS after cyclophosphamide treatment. Methods: We performed a historical prospective study in a cohort of MS patients treated with cyclophosphamide. We collected demographic data and medical history from medical databases and patient interviews. Reported cancers were histologically confirmed. Cancer incidence was compared with the incidence in the general population by estimating standardized incidence ratios (SIRs). Results: We included 354 patients, with a median follow-up of 5 years (range 2–15) after cyclophosphamide treatment. Fifteen patients developed a solid cancer, which occurred at a median of 3 years (range 0.5–14) after cyclophosphamide introduction. The cumulative incidence of cancer after cyclophosphamide was 3.1% at 5 years and 5.9% at 8 years. We found no increase in cancer incidence after cyclophosphamide treatment in men (SIR = 0.83, 95% confidence interval [CI] 0.30–1.82), women (SIR = 0.99, 95% CI 0.43–1.95), or men and women combined (SIR = 0.92, 95% CI 0.50–1.54). Conclusion: We found no evidence of an increased risk of cancer associated with cyclophosphamide treatment in MS patients.
