Eltrombopag for the treatment of inherited thrombocytopenias: a phase 2 clinical trial

Patients with inherited thrombocytopenias often require platelet transfusions to raise platelet count before surgery or other invasive procedures; moreover, subjects presenting 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 conducted a prospective, phase 2 clinical trial to investigate the efficacy of the oral thrombopoietin-mimetic eltrombopag in different forms of inherited thrombocytopenia. We enrolled 24 patients affected with MYH9-related disease, ANKRD26-related thrombocytopenia, X-linked thrombocytopenia/Wiskott-Aldrich syndrome, monoallelic Bernard-Soulier syndrome, or ITGB3-related thrombocytopenia. Average pre-treatment platelet count was 40.4 x109/L. Patients received a 3- to 6-week course of eltrombopag in a dose-escalation manner. Of 23 patients evaluable for response, 11 (47.8%) achieved a major response (platelet count >100 x109/L), 10 (43.5%) a minor response (platelet count at least twice than baseline), whereas 2 patients (8.7%) did not respond. Average increase of platelet count compared to baseline was 64.5 x109/L (p<0.001). Four patients who presented clinically significant spontaneous bleeding were admitted to a long-term eltrombopag administration (16 additional weeks): all of them obtained remission of mucosal hemorrhages that persisted throughout the treatment period. Treatment was globally well tolerated: 5 patients reported mild adverse events and one patient a moderate adverse event. In conclusion, eltrombopag was safe and effective in increasing platelet count and reducing bleeding symptoms in different forms of inherited thrombocytopenia. Despite these encouraging results, caution is recommended when using thrombopoietin-mimetics in inherited thrombocytopenias predisposing to leukemia. ClinicalTrials.gov identifier: NCT02422394.