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Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials

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Bussel, J, Arnold, DM, Grossbard, E, Mayer, J, Trelinski, J, Homenda, W, Hellmann, A, Windyga, J, Sivcheva, L, Khalafallah, AA, Zaja, F, Cooper, N, Markovtsov, V, Zayed, H and Duliege, A-M 2018 , 'Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials' , American Journal of Hematology, vol. 93, no. 7 , pp. 921-930 , doi: 10.1002/ajh.25125.

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Abstract

Spleen tyrosine kinase (Syk) signaling is central to phagocytosis-based, antibody-mediated platelet destruction in adults with immune thrombocytopenia (ITP). Fostamatinib, an oral Syk inhibitor, produced sustained on-treatment responses in a phase 2 ITP study. In two parallel, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n = 101) or placebo (n = 49) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks. The primary endpoint was stable response (platelets ≥50 000/μL at ≥4 of 6 biweekly visits, weeks 14-24, without rescue therapy). Baseline median platelet count was 16 000/μL; median duration of ITP was 8.5 years. Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P = .0003). Overall responses (defined retrospectively as ≥1 platelet count ≥50 000/μL within the first 12 weeks on treatment) occurred in 43% of patients on fostamatinib vs. 14% on placebo (P = .0006). Median time to response was 15 days (on 100 mg bid), and 83% responded within 8 weeks. The most common adverse events were diarrhea (31% on fostamatinib vs. 15% on placebo), hypertension (28% vs. 13%), nausea (19% vs. 8%), dizziness (11% vs. 8%), and ALT increase (11% vs. 0%). Most events were mild or moderate and resolved spontaneously or with medical management (antihypertensive, anti-motility agents). Fostamatinib produced clinically-meaningful responses in ITP patients including those who failed splenectomy, thrombopoietic agents, and/or rituximab. Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis.

Item Type: Article
Authors/Creators:Bussel, J and Arnold, DM and Grossbard, E and Mayer, J and Trelinski, J and Homenda, W and Hellmann, A and Windyga, J and Sivcheva, L and Khalafallah, AA and Zaja, F and Cooper, N and Markovtsov, V and Zayed, H and Duliege, A-M
Journal or Publication Title: American Journal of Hematology
Publisher: Wiley-Liss
ISSN: 0361-8609
DOI / ID Number: 10.1002/ajh.25125
Copyright Information:

Copyright 2018 The AuthorsLicensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)https://creativecommons.org/licenses/by-nc/4.0/

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