Early Treatment Use of Fostamatinib for Immune Thrombocytopenia (ITP): Efficacy and Safety As Second/Third ITP Treatment Lines in Clinical Practice in Spain
Authors: Gonzalez-Lopez Tomas Jose , Bermejo-Vega Nuria , Cardesa-Cabrera Rocío , Acedo Dominguez Natalia , Luis-Navarro Josefa , Lakhwani Sunil , Bernat Silvia , Haces-Tirado Guillermo Enrique , Galán Pilar , Lozano Maria Luisa , Martinez Carballeira Daniel , Hernandez Roberto , Jimenez Barcenas Reyes , Navas-Elorza Begoña , Marcellini Shally , Torres-Tienza Ana , Perona Blazquez Alvaro , Benet Carmen , Fernandez-Jimenez Dolores , López-Santamaría Castro Carolina , Jarque Isidro , Martínez Robles Violeta , González-Gascón-y-Marín Isabel , García-Donas Gabaldón Gloria 
Published: December 2024

Introduction: Fostamatinib is a splenic tyrosine kinase (SYK) inhibitor that prevents antibody-mediated platelet destruction. This drug has been shown to be effective and safe in immune thrombocytopenia (ITP) and is recommended as a second-line treatment with robust evidence by the International Working Group Consensus (IWG; 2019). Nevertheless, limited real-world data exist on its use as an early therapy for ITP (second/third ITP treatment lines).
Aims: The aim of this study was to evaluate data from daily clinical practice data on the treatment of adult ITP patients with fostamatinib in early lines of treatment: second (after steroids +/- intravenous immunoglobulin use [IVIG]) and third lines (after steroids +/- IVIG and another additional ITP therapy).
Methods: Multicentre, retrospective and prospective observational study at national level to evaluate the management of fostamatinib (Tavlesse®) in adult patients with ITP. An analysis of the medical records of all patients with ITP treated with fostamatinib at each center was performed. A total of 157 adult patients with ITP from 42 Spanish centers were treated with fostamatinib. Response was defined as a platelet count ≥ 30 x 109/L and at least two-fold increase the baseline count and absence of bleeding.Complete response was defined as a platelet count ≥ 100 x 109/L and absence of bleeding.
Results: We evaluated 64 of the 157 patients, in which fostamatinib was used as a second (n=21) or third ITP treatment lines (n=43). The median age of our cohort was 65 years (interquartile range, IQR, 57-77). 35/64 (54.7%) were female. Fifty-seven of them were primary ITP, 7 secondary ITP (2 lymphoproliferative disorders, 1 MGUS, 1 SLE, 2 SAF and 1 ITP secondary to HIV/HCV). 31/64 (48.4%) had ≥ 1 comorbidity of the Charlson Comorbidity lndex. At the time of ITP diagnosis, the median platelet count was 20 x 109 /L (IQR, 7-39) while 40 (62.5%) patients had hemorrhages (37/40 were mucocutaneous). The median time with a diagnosis of ITP at initiation of fostamatinib was 19 months (IQR, 4-114). 16 (25%) and 11 (17.2%) patients were newly-diagnosed and persistent ITP respectively, whereas 37 patients were diagnosed as chronic ITP.
Of the entire cohort of 64 patients, 27 (42.2%) were exposed to eltrombopag, 22 (34.4%) to IVIG, 6 (9.3%) to romiplostim and 4 (6.2%) to rituximab. Only 3 (4.7%) and 2 (3.1%) patients received splenectomy and avatrombopag prior to fostamatinib treatment, respectively. Nineteen patients (29.7%) had signs/symptoms of bleeding in the month prior to treatment initiation. 37/64 (57.8%) patients were treated with fostamatinib monotherapy throughout ITP. The median platelet count at baseline on fostamatinib was 25 x 109 /L (IQR, 12-57), while the median platelet count to best response achieved after fostamatinib treatment was 140 x 109 /L (IQR, 75-230 ). The median time from initiation of fostamatinib to maximum response to treatment was 63 days (IQR, 16-130). Similarly, the median duration of treatment with fostamatinib was 278 days (IQR, 130-449). 36 (56.2%) patients increased fostamatinib dose to 150 mg twice a day during fostamatinib therapy. The median time from initiation of fostamatinib to this dose increase was 26 days (IQR, 15-42).
A total of 55/64 patients (85.9%) responded to fostamatinib with 45/64 patients (70.3%) achieving a complete response. Regarding second line treatment, 17/21 patients (80.9%) responded to fostamatinib with 14 (66.6%) attaining complete responses. 38/43 patients (88.4%) responded as third line therapy with 31 (72.1%) achieving complete responses.
Twenty-nine patients (45.3%) experienced adverse events (AEs). The most frequent AEs were mild and moderate: diarrhea (n=11), hypertension (n=9) and cephalea (n=5). Fifteen patients (23.4%) discontinued fostamatinib treatment due to the following reasons: inefficacy to drug treatment (n=6, 9.4%), toxicity/severe adverse events (n=5, 7.8%), sustained response off-treatment (SROT) (n=3, 4.7%), and exitus non-related to fostamatinib use (n=1, 1.6%).
Conclusions: In this real-world study, fostamatinib showed high response rates when used as early treatment in ITP. In addition, fostamatinib showed a favourable safety profile in unselected patients with ITP.