CO092 | FOSTAMATINIB IN CHRONIC IMMUNE THROMBOCYTOPENIA: A REAL-WORLD MONOCENTRIC EXPERIENCE

M. Biglietto, S. Sorella, S. Ligia, S. Santostefano, R. Celia, R. Mormile, E. Baldacci, A. Chistolini, C. Santoro | Sapienza University of Roma, Italy

Background and aims. Fostamatinib, an inhibitor of spleen tyrosine kinase, has become a valuable therapeutic option for chronic ITP as a second or subsequent line of treatment. Our analysis aims to evaluate its efficacy and safety in the real-world setting.
Methods. We retrospectively analyzed 43 consecutive adult patients (> 18 years) with chronic ITP treated with fostamatinib in our center. Efficacy was evaluated as time to treatment failure (TTF); data were censored for patients who did not relapse until the last follow-up or who discontinued treatment for reasons other than loss of efficacy. Clinical response was categorized according to the international consensus criteria by Rodeghiero et al. (2009). Safety was assessed by monitoring treatment-emergent adverse events, with a focus on infections, arterial hypertension, diarrhea, and thrombotic events. Infections were defined severe if they required hospitalization. Patients were stratified by therapy line in Group 1 (1-2 prior treatment lines) and Group 2 (> 3 prior treatment lines). Statistical analysis was performed with SPSS26 using Kaplan-Meier curves and the log-rank test. Statistical significance was set at p <0.05.
Results. Thirty patients (69.8%) were female, and 13 (30.2%) were male. Prior to fostamatinib, patients had received a median of 4 therapy lines (range 2-12). All patients had been previously treated with corticosteroids (100%), while 21 (48.8%) received eltrombopag, 15 (34.9%) rituximab, 13 (30.2%) romiplostim, 8 (18.6%) avatrombopag, 6 (14.0%) splenectomy, 5 (11.6%) azathioprine, and 1 (2.3%) cyclosporine A. Twenty-three patients (53.4%) had a concomitant autoimmune diathesis, including Hashimoto thyroiditis (18.6%), persistent antiphospholipid antibody positivity (9.3%), antiphospholipid syndrome (7%), systemic lupus erythematosus (7%), multiple sclerosis (4.7%), common variable immunodeficiency (2.3%), Crohn's disease (2.3%), and Raynaud phenomenon (2.3%). Seven patients (16.3%) had previous thrombosis. Median age at fostamatinib start was 55 years (range 25-80). The median duration of fostamatinib treatment was 282 days (range 26-1319). The overall response rate (ORR) was 90.7%, with a complete response rate (CR) of 67.4%. Thirty-five patients (81.4%) received concomitant ITP treatments (15 corticosteroids, 12 TPO-RAs+corticosteroids, 6 TPO-RAs, and 2 rituximab+corticosteroids). Twelve patients (27.9%) discontinued fostamatinib due to non-response or loss of response, and two patients (4.7%) due to diarrhea; one patient (2.3%) tapered and discontinued fostamatinib, maintaining a response to therapy. No patients discontinued treatment due to arterial hypertension. No thrombotic events were reported. Severe infections occurred in 2 patients (4.7%), none of which led to permanent drug discontinuation. Kaplan-Meier analysis showed that therapy line is a significant predictor of response durability. Patients in Group 1 achieved a significantly longer median TTF compared to Group 2 (not reached vs. 112 days) (log-rank p=0.026) (Figure 1).
Conclusions. Fostamatinib proved to be safe and effective in our monocentric experience with a median follow-up of about 10 months (16/43 patients with a drug exposure of more than a year). The use of fostamatinib as a second/third line of treatment led to a significantly more durable response, supporting its early use in the ITP treatment algorithm.