Table 1.

Prevalence of malignancies under S1P₁-RM treatment

Drug	Trials/duration	Malignancies prevalence
Fingolimod	[3] FREEDOMS 24 months [5] TRANSFORM 12 months	• 0.5 mg group (n = 429)  o Basal cell carcinoma, n = 4 (0.9%) • 1.25 mg group (n = 425)  o Basal cell carcinoma, n = 1 (0.2%)  o Breast cancer, n = 1 (0.2%)  o Malignant melanoma, n = 1 (0.2%)  o Bowen’s disease, n = 1 (0.2%) • Placebo group (n = 418)  o Basal cell carcinoma, n = 3 (0.7%)  o Breast cancer, n = 3 (0.7%)  o Malignant melanoma, n = 1 (0.2%)  o Cervical carcinoma stage 0, endometrial cancer, n = 1 (0.2%)  o Prostate cancer, n = 1 (0.2%) • 0.5 mg group (n = 429)  o Melanocytic nevus, n = 28 (6.5%)  o Basal cell carcinoma, n = 3 (0.7%)  o Melanoma (including in situ), n = 3 (0.7%)  o Breast cancer, n = 2 (0.5%) • 1.25 mg group (n = 420)  o Melanocytic nevus, n = 42 (10.0)  o Basal cell carcinoma, n = 2 (0.5%)  o Melanoma (including in situ), n = 0  o Breast cancer, n = 2 (0.5%) • Interferon beta-1a n = 431  o Basal cell carcinoma, n = 1 (0.2%)  o Melanoma (including in situ), n = 0  o Breast cancer, n = 0
Fingolimod	[7] INFORMS 36 months	• 0.5 mg group (n = 336)  o Basal cell carcinoma, n = 14 (4%)  o Squamous cell carcinoma of skin, n = 6 (2%)  o Malignant melanoma (including in situ), n = 1 (< 1%)  o Breast cancer, n = 1 (< 1%)  o Invasive lobular breast carcinoma, 0  o Non-Hodgkin lymphoma, 1 (< 1%)  o Lung neoplasm, malignant, 1 (< 1%)  o Ovarian cancer, 1 (< 1%)  o Prostate cancer, 1 (< 1%) • Placebo group (n = 487)  o Basal cell carcinoma, n = 9 (2%)  o Squamous cell carcinoma of skin, n = 1 (< 1%)  o Malignant melanoma (including in situ), n = 0  o Breast cancer, n = 0  o Invasive lobular breast carcinoma, n = 1 (< 1%)  o Non-Hodgkin lymphoma, n = 0  o Lung neoplasm, malignant, n = 0  o Ovarian cancer, n = 0  o Prostate cancer, n = 1 (< 1%)
Siponimod	[15] BOLD 24 months [16] EXPAND 36 months	• 0.25 mg group (n = 50)  o None • 0.5 mg group (n = 29)  o Cervix neoplasm n = 1, (3.4%) • 1.25 mg (n = 43)  o Basal cell carcinoma, n = 1 (2.3%) • 2 mg (n = 29)  o None • 10 mg (n = 33)  o None • 0.5 to 2 mg (n = 1099)  o Skin neoplasms, malignant and unspecified, n = 14 (1%)  o Basal cell carcinoma, n = 11 (1%) • Placebo (n = 546)  o Skin neoplasms, malignant and unspecified, n = 8 (1%)  o Basal cell carcinoma, n = 6 (1%)
Ozanimod	[17] RADIANCE 24 months [18] SUNBEAM 12 months	• 0.5 mg (n = 439)  o Malignant melanoma in situ, n = 1 (0.2%)  o Medulloblastoma, n = 1 (0.2%)  o Basal cell carcinoma, n = 1 (0.2) • 1.0 mg (n = 434)  o Invasive breast carcinoma, n = 1 (0.2%)  o Keratoacanthoma, n = 1 (0.2%)  o Basal cell carcinoma, n = 1 (0.2%)  o Brest cancer, n = 1(0.2%) • Interferon beta-1a (n = 440)  o Chronic lymphocytic leukemia, n = 1 (0.2%)  o Basal cell carcinoma, n = 1 (0.2%) • 0.5 mg (n = 453)  o Invasive breast carcinoma and basal cell carcinoma, n = 2 (0.4%) • 1.0 mg (n = 448)  o Testicular seminar, n = 1 (0.2%) • Interferon beta-1a (n = 445)  o None
Ponesimod	[11] OPTIMUM 48 months	• Ponesimod 20 mg (n = 565)  o Skin malignant condition, n = 5 (0.9%)  o Non skin malignant condition, n = 1 (0.2%) • Teriflunomide 14 mg (n = 566)  o Skin malignant condition, n = 1 (0.2%)  o Non skin malignant condition, n = 1 (0.2%)