clinical study insights

Long-Term Efficacy and Safety of the Thrombopoietin Receptor Agonist Eltrombopag

by Howard A. Liebman, MD

Overview

Clinical Study Title:
Safety and Efficacy of Long-term Treatment of Chronic/Persistent ITP With Eltrombopag: Final Results of the EXTEND Study

Clinical Study Abstract:
In phase 2/3 trials, eltrombopag treatment of 6 months or less in patients with chronic/persistent immune thrombocytopenia (ITP) increased platelet counts and reduced bleeding. The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study. For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years (2 days-8.76 years). Median platelet counts increased to 50 × 109/L or more by week 2 and were sustained throughout the treatment period. Overall, 259 patients (85.8%) achieved a response (platelet count ≥50 × 109/L at least once in the absence of rescue), and 133 (52%) of 257 patients achieved a continuous response of 25 weeks or longer. Responses in patients with platelet counts lower than 15 × 109/L, more previous therapies, and/or splenectomy were somewhat lower. Thirty-four (34%) of 101 patients receiving concomitant ITP medication discontinued 1 or more medication. In patients with assessments, bleeding symptoms (World Health Organization grades 1-4) decreased from 57% at baseline to 16% at 1 year. Forty-one patients (14%) withdrew because of adverse events. Hepatobiliary adverse events (n = 7), cataracts (n = 4), deep vein thrombosis (n = 3), cerebral infarction (n = 2), headache (n = 2), and myelofibrosis (n = 2) occurred in more than 1 patient; the remaining adverse events occurred only once. Rates of thromboembolic events (6%) and hepatobiliary adverse events (15%) did not increase with treatment duration past 1 year. EXTEND demonstrated that long-term use of eltrombopag was effective in maintaining platelet counts of 50 × 109/L or more and reducing bleeding in most patients with ITP of more than 6 months’ duration. Important adverse events (eg, thrombosis, hepatobiliary, and bone marrow fibrosis) were infrequent.

Reference:
Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study [published correction appears in Blood. 2018;131(6):709]. Blood. 2017;130(23):2527-2536.

Expert Commentary

Howard A. Liebman, MD

Donald I Feinstein Chair in Medicine
Professor of Medicine and Pathology
Jane Anne Nohl Division of Hematology
USC Norris Cancer Hospital
Los Angeles, CA

“Data such as these concerning the long-term use of TPO-RAs have changed the whole treatment paradigm in chronic ITP because they allow patients to stop taking corticosteroids earlier and to maintain a safe platelet count long-term. I am able and willing to treat my patients with a TPO-RA for an extended period of time, and I have patients who have been taking a TPO-RA for many years.”

Howard A. Liebman, MD

Due to the chronic nature of ITP, most patients need prolonged treatment. Since treatment with a thrombopoietin receptor agonist (TPO-RA) may be needed for many years, it is important to understand the long-term efficacy and safety of these drugs. The EXTEND study was a long-term extension study of eltrombopag that began in 2006 and ended in 2015. Results of the study showed that eltrombopag was safe and effective in patients for up to 8 years of treatment. It was well tolerated, and the most frequently reported adverse events were headache, nasopharyngitis, and upper respiratory tract infection.

TABLE

Because the TPO-RAs have data such as these with extension studies out to over 5 years, we have a lot of long-term data on these treatments and we understand the toxicities and complications associated with them. Data such as these concerning the long-term use of TPO-RAs have changed the whole treatment paradigm in chronic ITP because they allow patients to stop taking corticosteroids earlier and to maintain a safe platelet count long-term. I am able and willing to treat my patients with a TPO-RA for an extended period of time, and I have patients who have been taking a TPO-RA for many years.

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