Background: Patients with acute myeloid leukaemia frequently have thrombocytopenia during induction chemotherapy. Eltrombopag, an oral thrombopoietin receptor agonist, stimulates platelet production by a similar mechanism to endogenous thrombopoietin. This study investigated safety and efficacy of eltrombopag versus placebo during anthracycline-based induction treatment of patients with acute myeloid leukaemia. Methods: In this randomised, double-blind, phase 2 study, treatment-naive patients were recruited from clinical centres across 10 countries (Australia, Belgium, Canada, Greece, Hungary, Israel, South Korea, Poland, Russia, and the USA). Patients with acute myeloid leukaemia of any subtype except M3 and M7 were stratified by antecedent malignant haematological disorder (yes or no) and age (18–60 years or >60 years) and were then randomly assigned (1:1) using an automated interactive voice–response system randomisation schedule. Investigators and patients were blinded to study treatment. Starting on day 4, patients received standard induction chemotherapy (daunorubicin bolus intravenous infusion on days 1–3 [90 mg/m 2 for patients aged 18–60 years or 60 mg/m 2 for patients aged >60 years], plus cytarabine continuous intravenous infusion on days 1–7 [100 mg/m 2 ]), with eltrombopag 200 mg (100 mg for east Asians) or placebo once daily, until platelet counts were 200 × 10 9 /L or higher, until remission, or after 42 days from the start of induction chemotherapy. The primary objective of the study was safety and tolerability assessed by adverse events, changes in left ventricular ejection fraction (LVEF), and clinical laboratory parameters in all treated patients. This study has been completed and is registered with ClinicalTrials.gov, number NCT01890746. Findings: Between Sept 7, 2013, and Jan 30, 2015, 149 patients were assessed for eligibility and 148 were then randomly assigned to receive eltrombopag (n=74) and placebo (n=74). Groups were matched in mean (SD) age (56·7 years [12·3] in the eltrombopag group vs 56·6 years [11·6] in the placebo group), mean (SD) initial platelet count (59·5 × 10 9 /L [43·3] vs 63·7 × 10 9 /L [48·0]), and poor-risk karyotype (16 [22%] of 74 patients in both groups). The most common grade 3–4 adverse events (≥10% in either group) were febrile neutropenia (31 [42%] vs 28 [39%]), decreased white blood cell count (8 [11%] vs 5 [7%]), and hypophosphataemia (3 [4%] vs 9 [13%]). Serious adverse events occurred in 24 (32%) patients in the eltrombopag group compared with 14 (20%) patients in the placebo group. 39 (53%) patients in the eltrombopag group died versus 29 (41%) patients in the placebo group. Thromboembolic events (5 [7%] vs 4 [6%]) and mean (SD) change in LVEF (−2·5% [7·8] vs −4·3% [8·5]) were similar. Interpretation: Data from this trial do not support combining eltrombopag with induction chemotherapy in patients with acute myeloid leukaemia. Funding: Novartis Pharma AG.
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