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Am J Hematol. 2018 Jul;93(7):921-930. doi: 10.1002/ajh.25125. Epub 2018 May 15.

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

Author information

1
Weill Cornell Medicine, New York, New York.
2
McMaster University, Michael G. DeGroote School of Medicine, and Canadian Blood Services, Hamilton, Ontario, Canada.
3
Rigel Pharmaceuticals, South San Francisco, California.
4
Fakultni nemocnice Brno, Brno, Czech Republic.
5
Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Łodzi, Lodz, Poland.
6
Wojewódzki Szpital Specjalistyczny im. J. Korczaka i Akademia Pomorska w Słupsku, Slupsk, Poland.
7
University Clinical Center, Medical University of Gdańsk, Gdańsk, Poland.
8
Instytut Hematologii i Transfuzjologii, Warszawa, Poland.
9
First Internal Department, MHAT Hristo Botev, AD, Vratsa, Vratsa, Bulgaria.
10
Menzies Institute for Medical Research, University of Tasmania, Launceston, Tasmania.
11
Clinica Ematologica, DAME, University of Udine, Udine, Italy.
12
Hammersmith Hospital, London, United Kingdom.

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.

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