Real-World Experience with Combination Therapy of Fostamatinib and Thrombopoetin Receptor Agonists (TPO-RAs) for Treatment of Immune Thrombocytopenia (ITP): Patient-Reported Outcomes

Background Immune thrombocytopenia (ITP) is a complex disease that ebbs and flows over time. Multiple mechanisms of disease may be present, including increased destruction of auto-antibody-bound platelets by macrophages, increased production of anti-platelet antibodies by B-cells, and decreased production of platelets by antibody-bound megakaryocytes. Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor that prevents platelet destruction and abrogates B-cell activation thereby decreasing plasma cell production of antibodies. Thrombopoietin receptor agonists (TPO-RA) stimulate megakaryocytes to increase production of platelets. The combination of these two drug classes has not been evaluated in randomized controlled trials. We retrospectively collected real-world data on patients with ITP treated with both fostamatinib and TPO-RAs. Methods Patients with ITP enrolled in a patient assistance program (PAP) associated with fostamatinib use were identified who had a) received fostamatinib for ≥30 days combined with ≥1 dose of TPO-RA (romiplostim, eltrombopag, or avatrompobag); b) ≥1 pre-treatment platelet count and ≥1 post-start-of-treatment platelet count; c) >3-month supply of fostamatinib with no more than a 60-day gap in treatment; and d) signed consent. Patients were registered for the PAP by their physician who provided baseline demographic and ITP-specific data, including platelet counts. A PAP nurse navigator then called patients every two weeks (or as agreed upon) to provide support and resources to patients regarding insurance coverage, medication adherence, and how/when to contact their provider as well as collect any platelet counts reported by the patient. Pre-specified study endpoints include median post-treatment platelet counts and the proportion of patients who achieved 1) platelet counts of ≥30,000/µL or ≥50,000/µL, 2) platelet counts of ≥30,000/µL or ≥50,000/µL on ≥50% of post-treatment readings, and/or 3) ≥1 post-treatment doubling of platelet count from the pre-treatment median and ≥30,000/µL. Results As of the data cutoff date (30 May 2024), 113 patients were eligible. The median age was 73 (range 24-100); 50 (44%) were male and 63 (56%) were female. The median platelet count at baseline was 24,000/µL (range 1000-346,000/µL) based on a median of 2 pre-treatment values (range 1-8). Fostamatinib was combined with romiplostim in 70 (62%) patients, eltrombopag in 27 (24%), avatrombopag in 9 (8%) and multiple TPO-RAs in 7 (6%). 90 patients (79.6%) increased their dose of fostamatinib to 150 mg BID, and 23 (20.4%) patients remained on fostamatinib 100 mg BID. Mean duration of fostamatinib therapy was 12.6 months (range 3-71). Patients reported a mean of 10 lab values (range 1-44; median 6) post-treatment start. Most patients (87%) achieved platelet counts of ≥30,000/µL at least once during treatment, and 73% had at least half their counts ≥30,000/µL. Most patients (83%) also achieved platelet counts ≥50,000/µL, and 60% had at least half their counts ≥50,000/µL. Most patients (75%) demonstrated ≥1 platelet count ≥30,000/µL and double their baseline, and 42% of patients had 50% or more of their post-treatment platelet counts ≥30,000/µL and double their baseline. Possible adverse events mentioned by patients via phone included diarrhea (23% of patients), increased blood pressure (18%), bruising/bleeding (12%), fatigue (8%), headache (5%), and thrombotic event (4%). Limitations of this real-world analysis include the potential for reporter bias since patients self-reported post-treatment platelet counts. Also, incomplete information about the dose regimen and stop date for TPO-RA precluded identification of patients who were truly receiving combination therapy versus those on bridge therapy from TPO-RA to fostamatinib. Also, real-world retrospective studies provide an incomplete assessment of safety, which is best evaluated in randomized controlled trials. Conclusions This real-world retrospective study included patients with ITP enrolled in a fostamatinib-associated patient support program. The study demonstrated that a combination of fostamatinib and TPO-RA were effective for the treatment of ITP and lead to a clinically meaningful response in a majority of patients. These results suggest that treating multiple mechanisms of disease using combination therapy may provide benefit to patients with an insufficient response to monotherapy.