Eltrombopag Delivers Clinical Benefit in Chronic Idiopathic Thrombocytopenic Purpura (ITP) Patients Not Achieving Platelet Counts ≥50,000/μL - Data from the EXTEND Study.

INTRODUCTION: Eltrombopag (PROMACTA^®/REVOLADE^®; GlaxoSmithKline, Collegeville, PA) is the first oral small molecule, non-peptide thrombopoietin receptor agonist shown to increase platelets and reduce bleeding symptoms during placebo-controlled trials in chronic ITP patients. EXTEND is an ongoing, open-label study designed to assess the long-term safety and clinical benefit of eltrombopag in patients with chronic ITP. While eltrombopag has been shown to raise platelet counts above the recognized goal of ≥50,000/μL in the majority of patients, it unknown whether patients who do not achieve this level of elevation derive other clinical benefit from eltrombopag therapy.

METHODS: For this analysis, patients who were enrolled in EXTEND for at least 6 weeks were evaluated to determine what percentage achieved platelet counts ≥50,000/μL from baseline platelet counts ≤30,000/μL. Furthermore, clinical benefit, in terms of doubled platelet counts, reduced bleeding symptoms, or reduced concomitant ITP medication use, was evaluated in the subgroup of patients who did not achieve platelet counts ≥50,000/μL during the study. Bleeding symptoms 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: Of the 117 patients with baseline platelet counts ≤30,000/μL evaluated, 91 patients (78%) achieved platelet counts ≥50,000/μL at least once during the study; whereas, 26 patients (22%) did not achieve platelet counts ≥50,000/μL. The majority of patients not achieving platelet counts ≥50,000/μL had baseline platelet counts ≤15,000/μL (96%, n = 24/26); however, 69% of all patients with baseline platelet counts ≤15,000/μL on study for at least 6 weeks achieved platelet counts ≥50,000/μL. The majority of patients not achieving platelet counts ≥50,000/μL during the study doubled their platelet count from baseline at least once (62%, n = 16/26). Among patients whose platelet counts doubled, the median baseline platelet count was 4,000/μL, compared to the median maximum platelet count of 29,000/μL achieved during treatment with eltrombopag. Nineteen of the 26 patients not achieving platelet counts ≥50,000/μL had bleeding symptoms at baseline (WHO Grades 1–4). The majority of the 19 patients with bleeding symptoms at baseline reduced their bleeding symptoms during treatment with eltrombopag (68%, n = 13/19). Eleven of the 26 patients not achieving platelet counts ≥50,000/μL were receiving concomitant ITP medications at baseline. Five of the 11 (45%) were able to reduce or discontinue at least 1 baseline concomitant ITP medication while receiving eltrombopag. A total of 24 of the 26 patients (92%) not achieving platelet counts ≥50,000/μL during the study derived clinical benefit (doubling of platelet count, reduction in bleeding, and/or reduction in use of concomitant ITP medications) following treatment with eltrombopag.

CONCLUSION: Approximately 80% of evaluated patients with baseline platelet counts ≤30,000/μL achieved platelet counts ≥50,000/μL during the study. In the subgroup of patients who did not achieve platelet counts ≥50,000/μL, clinical benefit was achieved by 92% of patients and consisted of doubled platelet counts, reduced bleeding symptoms, and/or reduced concomitant medication use.