The Safety and Efficacy of Fostamatinib in Patients with Chronic Immune Thrombocytopenic Purpura Treated in a Real-World Community Hematology Setting

Background: Chronic immune thrombocytopenia (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment with corticosteroids is intended to suppress the immune response and is effective in many patients but not sustainable. Fostamatinib is an approved therapy for adult patients with ITP who have had an insufficient response to a prior treatment. It is an oral small molecule that targets spleen tyrosine kinase (SYK), which has important roles in cellular proliferation, differentiation, and immune regulation. By blocking SYK, fostamatinib reduces the immune system's destruction of platelets, which allows the platelet (PLT) count to rise, thereby reducing the risk of bleeding in ITP patients. Two placebo-controlled randomized trials demonstrated that fostamatinib was well tolerated and able to induce meaningful platelet responses in heavily pretreated patients, as well as in earlier lines of therapy. The use of fostamatinib in a community hematology setting has not been evaluated. In this study, the real-world utilization and treatment patterns of fostamatinib in patients treated within the QCCA, a network of 17 community hematology clinics across the United States, is presented.

Methods: The QCCA network real world database was reviewed for ITP patients who had received fostamatinib over the past 3 years. Data collection consisted of patient demographics, disease characteristics, duration of ITP, existing comorbidities, number and type of prior ITP treatments and PLT count at baseline prior to the start of fostamatinib. All of the information was collected via a standardized data collection form. From the first day until the end of treatment, data were collected on hemoglobin, white blood cells, absolute neutrophil counts, PLT counts, concomitant ITP therapies and the use of rescue IVIG. A meaningful increase in PLTs was defined as achievement of platelet counts ≥ 30 and ≥ 50 x 10³/μL over the course of therapy.

Results: The medical records of the 46 ITP patients who met the inclusion criteria and received fostamatinib were evaluated. Patients had a median age of 58 years, 65% were female and 35% had a splenectomy. All patients had prior exposure to corticosteroids and the median number of therapies before stating fostamatinib was two. In addition, 65% had received thrombopoietin receptor agonists and rituximab. All patients started therapy at a dose of 100 mg twice daily for a median duration of 2 months (interquartile range [IQR] = 1 to 15) and a mean duration of 6.7 months (95%CI: 3.5 to 9.9). When fostamatinib was started, the median PLT count was 19 x 10³/μL (IQR = 3 to 70). From the start of therapy, the maximum increase in the median PLT count was 78 x 10³/μL (IQR = 13 to 231), which was achieved after a median of 1.8 months. Over the course of therapy, 31 (67.4%) and 26 (56.5%) of 46 patients achieved or maintained PLT levels ≥ 30 and ≥ 50 x 10³/μL respectively. Of note, prior to the start of fostamatinib, 9 and 7 patients respectively, already had PLT levels ≥ 30 and ≥50 x 10³/μL. The percent of patients with at least a doubling of their baseline PLT count was 47.8% (95%CI: 32.9 to 63.0%). There were no serious bleeding events reported, and only one patient required the discontinuation of fostamatinib because of adverse events. Among the 46 patients, 16 received concomitant IVIG to increase PLT counts.

Conclusions: In this real-world setting, the findings suggest that fostamatinib is safe and effective in patients with chronic ITP who had relapsed or had not responded to one or more prior treatments.

Kreychman:Rigel Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company.