Abstract Number: PB1358
Meeting: ISTH 2020 Congress
Theme: Platelet Disorders and von Willebrand Disease » Acquired Thrombocytopenias
Background: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by platelet destruction. Autoantibodies bind to platelet antigens leading to platelet phagocytosis by Fcγ receptor bearing macrophages that requires spleen tyrosine kinase (SYK) signaling. Fostamatinib, an oral SYK inhibitor, was approved for the treatment of ITP based on phase 3 studies in adults with persistent and chronic ITP. As autoimmune diseases develop chronicity, they can become harder to manage due to longitudinal epitope spreading, increased autoantibody titer, and associated complement and T cell involvement. Early treatment of autoantibody-mediated diseases like ITP with drugs targeting corresponding pathways, such as Fcγ receptor driven phagocytosis, could produce better outcomes.
Aims: We conducted a post hoc analysis of the phase 3 studies to evaluate the response of patients who received fostamatinib as second-line therapy and those with disease < 2 years.
Methods: 145 adults with ITP received fostamatinib 100mg BID which was increased to 150mg BID after 4 weeks if platelets were < 50,000/µL. A platelet response was ≥1 platelet count ≥50,000/µL at any visit without rescue. Second-line therapy patients previously received steroids +/- immunoglobulins.
Results: Fostamatinib was second-line therapy for 32 patients (baseline characteristics in Table 1). A platelet response occurred in 25/32 (78%) patients compared with 47% of later line therapy patients. Adverse events (Table 2) were consistent with that of the overall study population.
A platelet response occurred in 9/10 (90%) patients with persistent ITP (< 1 year) and 11/19 (57%) patients with 1 to < 2 years ITP. The whole phase 3 population had a 54% platelet response rate.
Conclusions: Fostamatinib use as second-line therapy or in earlier stage disease for ITP may be more effective than as later-line therapy or in later stage disease.
| Baseline Characteristic | Fostamatinib as second-line therapy (n=32) | Fostamatinib exposure population (N=145) |
| Age, median (range) in years | 50 (20-88) | 53 (20-88) |
| Duration of ITP, median (range) in years | 2.7 (<1-50) | 8.4 (<1 -53) |
| ITP classification (%) Persistent (<1 year) | 5 (16%) | 10 (7%) |
| ITP classification (%) Chronic (≥1 year) | 27 (84%) | 135 (93%) |
| Baseline platelet count, median (/µL) | 21,500 | 16,000 |
| All patients provided written informed consent prior to study and the study protocol was reviewed and approved by an independent ethics committee. | ||
[Table 1. Baseline Characteristics]
| Most Common AEs | Mild | Moderate | Severe | Total |
| Hypertension | 6 (19%) | 4 (13%) | 0 | 10 (31%) |
| Diarrhea | 3 (9%) | 5 (16%) | 0 | 8 (25%) |
| Upper respiratory tract infection | 2 (6%) | 3 (9%) | 0 | 5 (16%) |
| Nausea | 4 (13%) | 0 | 0 | 4 (13%) |
| Vomiting | 3 (9%) | 1 (3%) | 0 | 4 (13%) |
| Petechiae | 3 (9%) | 1 (3%) | 0 | 4 (13%) |
| Headache | 1 (3%) | 3 (9%) | 0 | 4 (13%) |
| Elevated alanine aminotransferase | 3 (9%) | 1 (3%) | 0 | 4 (13%) |
| Elevated aspartate aminotransferase | 3 (9%) | 1 (3%) | 0 | 4 (13%) |
[Table 2. Common adverse events for the 32 second-line therapy patients]
To cite this abstract in AMA style:
Ghanima W, Cooper N, Boccia R, Boxer M, Hill Q, Sholzberg M, Tarantino M, Kreychman Y, Markovtsov V, Tong S, Bussel J. Fostamatinib as Second-Line Therapy for ITP and in Earlier Stage ITP Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/fostamatinib-as-second-line-therapy-for-itp-and-in-earlier-stage-itp-patients/. Accessed November 29, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/fostamatinib-as-second-line-therapy-for-itp-and-in-earlier-stage-itp-patients/