Fostamatinib and Thrombopoietin Receptor Agonists to Optimize Personalized Chronic Immune Thrombocytopenia Management

Key mechanisms underlying immune thrombocytopenia (ITP) pathophysiology include impaired platelet production and macrophage-mediated platelet destruction, the latter of which is the disease driver in more than half of patients. Traditional sequential treatment approaches achieve suboptimal responses in many patients. This review summarizes ITP pathogenesis and the treatment landscape and proposes a personalized treatment approach for ITP based on underlying disease mechanisms to optimize care with immunomodulatory and bone marrow-supportive therapies (fostamatinib, rituximab, and thrombopoietin receptor agonists [TPO-RAs]). Clinical evidence of monotherapy and real-world studies of combination therapy are reviewed to support mechanism-based treatment selection, focusing on the complementary actions of fostamatinib (to target platelet destruction) and TPO-RAs (to stimulate platelet production). In prior studies, fostamatinib with or without TPO-RAs demonstrated durable platelet responses and manageable safety as second-line or later ITP treatment. The proposed treatment framework augments guidelines by recommending fostamatinib, rituximab, or TPO-RAs as second-line therapy options based on patient-specific disease characteristics and risks. Patients with inadequate response to fostamatinib or TPO-RA monotherapy may combine these therapies to address both platelet destruction and platelet production deficits. This novel mechanistic framework enables optimization of safety and efficacy based on patient-specific pathophysiology to support individualized care.