Page 306 - Haematologica March 2020

Ferrata Storti Foundation
Haematologica 2020 Volume 105(3):820-828
Platelet Biology & its Disorders
Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial
Carlo Zaninetti,1,2 Paolo Gresele,3 Antonella Bertomoro,4 Catherine Klersy,5 Erica De Candia,6,7 Dino Veneri,8 Serena Barozzi,1 Tiziana Fierro,3 Maria Adele Alberelli,6 Valeria Musella,5 Patrizia Noris,1 Fabrizio Fabris,4 Carlo L. Balduini1,9 and Alessandro Pecci1
1Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation and
University of Pavia, Pavia; 2PhD course in Experimental Medicine, University of Pavia,
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Pavia; Department of Medicine, University of Perugia, Perugia; Department of Medicine,
University of Padova, Padova; 5Service of Clinical Epidemiology & Biometry, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia; 6IRCCS Policlinico Universitario A. Gemelli Foundation, Roma; 7Institute of Internal Medicine and Geriatrics, Catholic University of the Sacred Heart, Roma; 8Department of Medicine, Section of Hematology, University of Verona, Verona and 9Ferrata-Storti Foundation, Pavia, Italy.
ABSTRACT
Patients with inherited thrombocytopenias often require platelet trans- fusions to raise their platelet count before surgery or other invasive pro- cedures; moreover, subjects with clinically significant spontaneous bleeding may benefit from an enduring improvement of thrombocytopenia. The hypothesis that thrombopoietin-mimetics can increase platelet count in inherited thrombocytopenias is appealing, but evidence is scarce. We con- ducted a prospective, phase II clinical trial to investigate the efficacy of the oral thrombopoietin-mimetic eltrombopag in different forms of inherited thrombocytopenia. We enrolled 24 patients affected by MYH9-related dis- ease, ANKRD26-related thrombocytopenia, X-linked thrombocytopenia/ Wiskott-Aldrich syndrome, monoallelic Bernard-Soulier syndrome, or ITGB3-related thrombocytopenia. The average pre-treatment platelet count was 40.4 x109/L. Patients received a 3- to 6-week course of eltrombopag in a dose-escalated manner. Of 23 patients evaluable for response, 11 (47.8%) achieved a major response (platelet count >100 x109/L), ten (43.5%) had a minor response (platelet count at least twice the baseline value), and two patients (8.7%) did not respond. The average increase of platelet count com- pared to baseline was 64.5 x109/L (P<0.001). Four patients with clinically sig- nificant spontaneous bleeding entered a program of long-term eltrombopag administration (16 additional weeks): all of them obtained remission of mucosal hemorrhages, with the remission persisting throughout the treat- ment period. Treatment was globally well tolerated: five patients reported mild adverse events and one patient a moderate adverse event. In conclu- sion, eltrombopag was safe and effective in increasing platelet count and reducing bleeding symptoms in different forms of inherited thrombocytope- nia. Despite these encouraging results, caution is recommended when using thrombopoietin-mimetics in inherited thrombocytopenias predisposing to leukemia. ClinicalTrials.gov identifier: NCT02422394.
Introduction
Inherited thrombocytopenias are a heterogeneous group of disorders characterized by a reduced number of blood platelets which can result in a bleeding tendency of variable severity. Although inherited thrombocytopenias are rare, recent improve- ments in the knowledge of these conditions have indicated that, taken together, their prevalence is higher than previously thought. In fact, based on a registry of patients with thrombocytopenia, the prevalence of inherited thrombocytopenias in the Italian population is estimated to be 2.7 cases per 100,000 population.1
Most patients with an inherited thrombocytopenia have mild or no spontaneous
Correspondence:
ALESSANDRO PECCI
alessandro.pecci@unipv.it
Received: April 8, 2019. Accepted: June 28, 2019. Pre-published: July 4, 2019.
doi:10.3324/haematol.2019.223966
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/3/820
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