An Observational Study of Fostamatinib As Second Line Therapy in Adult Patients with Immune Thrombocytopenia (ITP) in Real-World Clinical Practice

Abstract Background: In immune thrombocytopenia (ITP), autoantibody-bound platelets are targeted for phagocytosis by Fcγ-receptors on macrophages in a spleen tyrosine kinase (SYK)-dependent signaling pathway. Fostamatinib is a potent oral SYK inhibitor that demonstrated efficacy for the treatment of ITP in two phase 3 randomized, placebo-controlled, double-blind studies and long-term durable responses in the phase 3 open-label extension study. In these studies, 146 patients with ITP were treated with fostamatinib, and 54% had a platelet response (platelet count ≥50,000/µL), which was maintained over a median of 86% of treatment days. These studies led to approval of fostamatinib in the US, Europe, and Canada as a therapy for chronic ITP in adult patients who have had an insufficient response to a prior treatment. Further, a post-hoc analysis showed that, in those who received fostamatinib as second-line therapy (following steroids ± immunoglobulins), 78% achieved a platelet response, which was maintained over a median of 83% of treatment days. 1 Adverse events (AEs) were reported in 72% of second-line patients and 86% of all patients, and common AEs were similar between second-line patients and the total patient population. 1, 2 Bleeding events were reported in 24% of second-line patients vs. 41% of all patients. The results of the post hoc analysis underscored the necessity for further evaluation of fostamatinib as a second-line therapy for ITP. We are conducting a multi-center, prospective, observational, two cohort study of fostamatinib as second-line therapy for the management of ITP in adult patients who have an insufficient response to prior steroids ± immunoglobulins. Aim: This study will evaluate clinical outcomes and safety of fostamatinib as second-line therapy for ITP in adult patients in real-world clinical practice. Patients will also be assessed for quality of life and utilization of health care resources during the study. Methods: The study (FORTE; NCT04904276; O-FOSTA-901) is being conducted at 10 sites across the US and will enroll 45 patients with ITP into 2 cohorts (see Figure). The study is registered at https://clinicaltrials.gov/ct2/show/NCT04904276. The study aims to enroll adult patients with a confirmed diagnosis of ITP and an inadequate response to prior steroids ± immunoglobulins. Patients who have received any prior ITP treatment other than steroids or immunoglobulins will be excluded. Patients who will initiate fostamatinib as second-line therapy at study entry will be enrolled into Cohort 1; patients currently receiving fostamatinib as second-line therapy with the intent to continue treatment will be enrolled in Cohort 2 (historical platelet counts will be retrospectively collected). Patients will be treated by their clinician at the clinician's discretion (not pre-specified by a study protocol). Primary outcome measures will include platelet count over time, duration of platelet count elevation, use of ITP rescue medication, changes in dosing, use of concomitant ITP medications, incidence of serious and ITP-related AEs, and quality of life. Quality of life assessments will utilize the SF-36v2 and ITP-PAQ. All data will be collected at regularly scheduled clinic visits according to the clinician's normal practice for 12 months or until fostamatinib is discontinued. Summary: This ongoing observational study of adult patients with ITP will enable further characterization of the risk/benefit profile of fostamatinib as a second-line treatment for ITP and will provide insight on how clinicians manage ITP in a real-world setting without the constraints of a clinical trial protocol. References 1. Boccia R, et al. Br J Haematol. 2020. 2. Bussel J, et al. Am J Hematol. 2019 Figure 1 Figure 1. Disclosures Hughes: Abbvie: Speakers Bureau; Rigel: Other: Advisory Board, Research Funding; Amgen: Speakers Bureau; Karyopharm: Other: Advisory Board, Speakers Bureau. Numerof: Rigel Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zider: Rigel Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Chow: Rigel Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Goel: Rigel Pharmaceuticals, Inc.: Consultancy; Alexion: Consultancy; NHLBI: Research Funding.

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