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- Title
(DXT74) An Analysis of the Relationship Between Cladribine Dose and Risk of Malignancies in Patients with Multiple Sclerosis.
- Authors
Cook, Stuart; Giovannoni, Gavin; Leist, Thomas P.; Comi, Giancarlo; Nolting, Axel; Sylvester, Elke; Jack, Dominic; Damian, Doris; Galazka, Andrew
- Abstract
Background: Malignancy risk was previously characterized in a monotherapy oral cohort of patients with multiple sclerosis (MS) treated with cladribine tablets (CTs) 10 mg (3.5 mg/kg cumulative dose over 2 years; referred to as CT3.5) including cumulative data up to February 2015. In clinical studies, an imbalance in the number of malignancies with CT3.5 vs placebo was observed, suggesting malignancy risk may be increased. Objectives: To provide a more detailed assessment of malignancy using safety data integrated from clinical trials and a safety follow-up registry (up to May 2017), to further characterize the malignancy risk of CTs in patients with MS and investigate whether there is a dose-dependent risk. Methods: Cohorts were monotherapy oral: patients with MS receiving CTs at any dose as a monotherapy; all exposed: patients with MS receiving any formulation of cladribine to provide a larger cohort to identify rare events such as malignancies. Results: In the monotherapy oral cohort, patient numbers (patient-years [PYs]) were: placebo N = 641 (2275), CT3.5 N = 923 (3754), CT 5.25 mg/kg (CT5.25) N = 632 (2610). The incidence per 100 PYs for malignant tumors during the entire follow up was: placebo: 0.13, CT3.5: 0.27, and CT5.25: 0.23. The risk difference vs placebo was: CT3.5: 0.14 (95% CI -0.14 to 0.38) and CT5.25: 0.10 (-0.18 to 0.39). In CLARITY CT3.5 and CT5.25 patients randomized to CT3.5 in CLARITY Extension (N = 195 for each treatment group), incidence per 100 PYs by CLARITY CT dose was: 0.55 (CT3.5, 1301 PYs) and 0.31 (CT5.25, 1286 PYs) for the entire follow-up; 0.91 (CT3.5, 790 PYs) and 0.52 (CT5.25, 784 PYs) for the period following initiation of treatment in year 3. An analysis of the all exposed cohort (cladribine N = 1976; placebo N = 802) stratified by cumulative cladribine dose gave the number of patients with a malignant event (incidence per 100 PY) as: >0--3.5 mg/kg = 6 (0.37), >3.5--5.25 = 14 (0.40), >5.25--7.0 = 6 (0.29), >7.0--8.75 = 6 (0.46), >8.75 = 2 (0.21). No hematological malignancies were observed at any time in the pooled dataset. Conclusions: Overall, there was no clear evidence of a dose effect of cladribine on malignancy risk in patients with MS based on >9500 PYs of cladribine exposure.
- Subjects
TUMOR risk factors; ADENOSINES; CLINICAL trials; CONFERENCES &; conventions; MULTIPLE sclerosis
- Publication
International Journal of MS Care, 2020, Vol 22, Issue S2, p42
- ISSN
1537-2073
- Publication type
Article