Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Treatment with fostamatinib in patients with immune thrombocytopenia: Experience from the Andalusian region in Spain-The Fostasur Study.

Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.

The influence of the age in the risk of the prothrombin G20210A mutation for spontaneous venous thrombosis.

BACKGROUND AND OBJECTIVE: Factor V Leiden mutation (FVL), and the prothrombin G20210A mutation (PT G20210A) are polymorphisms with a weak risk factor for venous thromboembolic disease. The probability of spontaneous venous thrombosis in carriers of thrombophilic mutations (FVL and PT G20210A) was analyzed. PATIENTS AND METHOD: We studied 735 individuals (407 were healthy controls and 328 patients with venous thrombosis) with respect to FVL and PT G20210A, determined by polimerase chain reaction in liquid phase, real time. chi2 test and logistic regression analysis were used to evaluate the results. The dates were analyzed with the statistical program SPSS v. 14.0. RESULTS: The carrier patients of PT G20210A mutation whose age was over 40 years had a risk factor for spontaneous venous thrombosis which was 9.28 (odds ratio [OR]) (95% confidence interval [CI], 3.01-28.60; p < 0.0005) times greater than carriers of the PT G20210A mutation who were 40 year-old or younger. In our patients, being male meant a weak risk factor for venous spontaneous thrombosis (p = 0.021; OR = 1.64; 95% CI, 1.08-2.51) . CONCLUSIONS: Our results demonstrate a potentiation of the thrombotic risk by an increase of age in the carriers of the PT G20210A mutation.