Two placebo-controlled phase 3 studies of fostamatinib, an oral spleen tyrosine kinase (Syk) inhibitor, for the treatment of persistent/chronic immune thrombocytopenia (ITP) in adults: Analysis of platelet response by prior ITP therapies.

e15146 Background: Syk is an important signaling molecule for autoantibody-mediated platelet [plt] destruction by macrophages in pathogenesis of ITP. In 2 identical placebo-controlled phase 3 studies, the oral Syk inhibitor fostamatinib showed a collective stable response rate (proportion of patients [pts] with plt count ≥50,000/mL at ≥4 of 6 visits w/o rescue therapy during weeks 14-24) of 18% (18/101) for fostamatinib vs 2% (1/49) for placebo (P= 0.0003). An overall response (≥1 plt count ≥50,000/mL) rate of 43% was achieved with fostamatinib, compared with 14% for placebo (P= 0.0006). Here we present responses by prior therapy and baseline plt count. Methods: We examined stable responses in pts on fostamatinib from the pooled phase 3 studies according to prior thrombopoietin-receptor agonists (TPO-RA), rituximab, splenectomy, or median baseline plt count, as well as overall responses by disease duration at study entry in the double-blind studies. Results: Pts had ITP of long disease duration (median 8.5 yrs) and median 3 (range, 1-13) prior unique ITP therapies, including 94% with corticosteroids, 47% TPO-RA, 32% rituximab, 35% splenectomy, and 44% other immunosuppressants. Median baseline plt count was 16,000/μL. Stable responses on fostamatinib were achieved in 7 of 46 (15%) with and 11 of 55 (20%) without prior TPO-RA, 4 of 34 (12%) with and 14 of 67 (21%) without prior rituximab, 6 of 34 (18%) with and 12 of 67 (18%) without prior splenectomy, and 6/47 (13%) and 12/54 (22%) with baseline plt counts < and ≥15,000/µL, respectively. Overall responses were seen across a wide range of ITP durations including those with a duration of < 3 years (52%), 3 to < 8 years (48%) and ≥8 years (36%), but with no apparent correlation with disease duration. Most adverse events on fostamatinib were mild or moderate; all resolved over time or with treatment. Conclusions: Syk inhibition with the investigational agent fostamatinib produced clinically meaningful responses in adult ITP pts, with no clear relationship found between plt response and prior ITP treatment or disease duration. Clinical trial information: NCT02076399, NCT02076412.

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