Figure 2. Incidence of malignancies and risk factor analysis.

(A) Standardized incidence ratios with exact 95% confidence intervals of any malignancy or single entities in mitoxantrone-treated patients with multiple sclerosis (n = 677; breast cancer [only females], n = 455) compared to the German general population (dashed line; data from Robert Koch Institute, Berlin, Germany), matched for age, sex, and year of occurrence. Note that increased frequencies are present for acute myeloid leukemia and for colorectal cancer. (B) Multivariate Cox regression analyzing potential malignancy risk factors in mitoxantrone-treated patients. Hazard ratios, 95% confidence intervals, and p values are depicted. The reported hazard ratio for age at treatment initiation refers to 5-year intervals and that for cumulative mitoxantrone dose to a comparison of patients having received >75 vs ≤75 mg/m². For definition of “other immunosuppressant,” see the Methods section. Note that only higher age at treatment initiation shows a significant elevation above the dashed line while other factors including higher cumulative dose do not seem to increase the risk.