Preview

PDF 127801 Journal ...pdf | Download (947kB) | Preview

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:	https://doi.org/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/
Related URLs:	UTAS Profile: Khalafallah, AA
Item Statistics:	View statistics for this item

Actions (login required)

Item Control Page