Safety and efficacy of long-term treatment with oral eltrombopag for chronic idiopathic thrombocytopenic purpura.

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Introduction: Eltrombopag (PROMACTA/REVOLADE; GlaxoSmithKline, Collegeville, PA) is the first oral, small molecule, non-peptide thrombopoietin receptor agonist under investigation for the treatment of thrombocytopenia due to various causes, including idiopathic thrombocytopenic purpura (ITP). Chronic ITP is characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to chronically low peripheral platelet counts. Eltrombopag treatment has previously demonstrated a significant increase in platelet counts and a reduction in clinically relevant bleeding symptoms in 2 placebo-controlled trials evaluating a total of >200 patients with chronic ITP after up to 6 weeks of treatment. EXTEND is an ongoing open-label, phase III extension study to assess the long-term safety and efficacy of oral eltrombopag in ITP patients that have previously completed an eltrombopag trial.

Methods: Patients with previously treated, chronic ITP who completed a prior eltrombopag study were eligible to participate in EXTEND. Eltrombopag treatment was initiated at 50 mg once daily and then adjusted in order to maintain platelet counts ≥ 50,000/μL and <400,000/μL, with doses between 75 mg once daily and 25 mg once daily or less often than once daily, if necessary. Patients who achieved platelet counts ≥ 50,000/μL during treatment with eltrombopag were considered responders. Bleeding events were prospectively evaluated using the WHO Bleeding Scale: Grade 0 = no bleeding, Grade 1 = mild bleeding, Grade 2 = moderate bleeding, Grade 3 = gross bleeding and Grade 4 = debilitating blood loss.

Results: At the time of this analysis, 207 patients (median age, 50 years; 67% female) had received eltrombopag on this study. At baseline, 33% were receiving concomitant ITP medication and 40% were splenectomized. The majority of patients (70%) enrolled with baseline platelet counts <30,000/μL, followed by 18% and 12% with baseline platelet counts from ≥ 30,000/μL to ≤ 50,000/μL, and >50,000/μL, respectively. The duration of eltrombopag treatment ranged from 3 to 523 days. Seventy-nine percent (159/201) of patients achieved a platelet count ≥ 50,000/μL, and 24% (18/75) of patients who had received eltrombopag for at least 25 weeks maintained platelet counts ≥ 50,000/μL continuously for ≥ 25 weeks. Patients responded to eltrombopag regardless of splenectomy status (non-splenectomized: 78%, splenectomized: 81%) and use of baseline concomitant ITP medications (no baseline ITP medications: 79%, baseline ITP medications: 80%). Median platelet counts remained ≥ 50,000/μL throughout the observation period of the study (Figure 1) with only 3 exceptions, when the median platelet counts remained >40,000/μL. At baseline, 59% of patients reported bleeding symptoms (WHO Grades 1–4) compared with approximately 30% at months 1, 3, and 6. Adverse events (AEs) were reported in 150 patients (72%) while on therapy, the majority of which were mild to moderate. Headache (15%) was the most commonly reported on-therapy AE, followed by upper respiratory tract infection (13%), diarrhea (10%), and nasopharyngitis (9%). Six thromboembolic events were reported during the study. No clinically relevant effects of eltrombopag on patient bone marrow were detected. Thirty-nine serious AEs were reported by 17 patients (8%) while on therapy +1 day. Four deaths were reported in the study (2 deaths on therapy and 2 deaths >30 days after the last dose of eltrombopag); none were considered related to study medication.

Conclusion: Oral eltrombopag is effective at raising platelet counts and decreasing bleeding symptoms during long-term treatment, regardless of splenectomy status or the use of baseline ITP medications. Eltrombopag is well tolerated during long-term treatment in patients with previously treated chronic ITP.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Blood, American Society of Hematology

DOI

https://doi.org/10.1182/blood.V112.11.3432.3432

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Link to Full Text

Share

COinS