Anne-Marie Duliege, MD
Almost half of adult patients with previously treated chronic immune thrombocytopenia (ITP) achieved major responses with the SYK inhibitor fostamatinib (Tavalisse), according to an analysis of pooled clinical study data.
Overall, 44% of patients achieved an objective response, defined as at least 1 platelet count ≥50,000/µL during the first 12 weeks of treatment without rescue medication. Patients treated with had a low risk of bleeding and a low need for rescue medication as compared with placebo-treated patients from randomized trials.
“Responders had increased platelet counts, reduced use of rescue medications, and reduced frequency of bleeding episodes,” Anne-Marie Duliege, MD, of Rigel Pharmaceuticals, reported at the 2018 ASH Annual Meeting. “Some patients who were not responders continued treatment for an extended period of time.
“Fostamatinib was well tolerated for an extended period of time. No new safety signals or cumulative toxicity was detected during long-tern treatment with fostamatinib.”
Fostamatinib received FDA approval in April 2018 for patients with ITP who responded inadequately to prior ITP therapy. Duliege reported findings from an updated analysis of 2 randomized trials and an open-label extension study, all of which supported the application for approval. The analysis included a total of 146 patients, 29% of whom remained on fostamatinib. The patients had a median follow-up of 7.2 months (range, 0.5-41.3). Seventy-one percent of patients had at least 6 months of follow-up, and 35% had ≥18 months of follow-up.
“The patients have 163 patient-years of fostamatinib exposure, as compared to 29 and 12 in the fostamatinib and placebo arms, respectively, during the randomized controlled trials,” she said.
Patients included in the analysis had a median age of 53 years (range, 20-88) and a median disease duration of 8.5 years (range, 0.3-53). They had a median of 3 (range, 1-13) prior treatments for ITP, most often corticosteroids (94%), thrombopoietin-receptor agonists (47%), and rituximab (Rituxan; 32%). Additionally, 35% of the patients had undergone splenectomy. The patients had a median baseline platelet count of 16,000/µL.
In the randomized trials, fostamatinib treatment led to a response rate of 43% compared with 14% in placebo-treated patients (P
= .0006). The updated analysis, which included all patients exposed to fostamatinib, yielded a response rate consistent with what was observed in the randomized trial. The 56% of patients who did not meet response criteria included some patients who had improved platelet counts that did not meet the definition for objective response.
Patients who responded to fostamatinib tended to be younger, have a shorter disease duration, were more likely to have persistent ITP as opposed to chronic ITP). Responders also had a higher baseline platelet count compared with nonresponders (20,000/µL vs 11,750/µL). Treatment history was similar between responders and nonresponders, although more nonresponders had undergone splenectomy (43% vs 25%).
Patients who responded to fostamatinib were significantly less likely to require rescue medication compared with those assigned to placebo. The exposure-adjusted incidence of rescue therapy use per patient-year was 0.26 among responders compared with 2.58 among nonresponders. Patients who received fostamatinib but did not meet response criteria had a rescue medication use incidence of 0.86 per patient-year.
The most common all-grade adverse events (AEs) were diarrhea (35%), hypertension (21%), nausea (19%), epistaxis (17%), and petechiae (15%). Severe AEs included diarrhea, petechiae, dizziness, and confusion (1% each). Duliege said 19% of patients discontinued treatment because of AEs, most often diarrhea (4%) and neutropenia (2%).
The incidence of serious adverse events (SAEs) was 27% (n = 39). The incidence of SAEs probably/possibly related to fostamatinib was 6%, consisting of diarrhea and neutropenia in 2 patients each and increased transaminase, atrial fibrillation, upper respiratory tract infection, sepsis, pneumonia, pyrexia, and hypertensive crisis in 1 patient each.
Duliege AM, Arnold D, Boccia R, et al. Two-year safety and efficacy outcomes with fostamatinib in adult patients with immune thrombocytopenia (ITP): open-label extension to the phase 3 trial program. Presented at: ASH Annual Meeting and Exposition; December 4-8, 2018; San Diego, CA. Abstract 736.