Frey N, et al. - Researchers analyzed the safety and effectiveness of eltrombopag vs placebo during anthracycline-based induction therapy of subjects with acute myeloid leukemia. Ultimately, they did not support the use of eltrombopag combined with induction chemotherapy in these patients.

Methods

• In this randomized, double-blind, phase 2 study, they recruited treatment-naive subjects from clinical centers across 10 countries ie, Australia, Belgium, Canada, Greece, Hungary, Israel, South Korea, Poland, Russia, and the USA.
• They stratified candidates with acute myeloid leukemia of any subtype except M3 and M7 by antecedent malignant hematological 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 randomization schedule.
• Researchers and subjects were blinded to study therapy.
• Starting on day 4, candidates were given standard induction chemotherapy (daunorubicin bolus intravenous infusion on days 1–3 [90 mg/m² for patients aged 18–60 years or 60 mg/m² for patients aged >60 years], plus cytarabine continuous intravenous infusion on days 1–7 [100 mg/m²]), with eltrombopag 200 mg (100 mg for east Asians) or placebo once daily, until platelet counts were 200 × 10m⁹/L or higher, until remission, or after 42 days from the start of induction chemotherapy.
• The primary outcome of the trial was safety and tolerability estimated by adverse events, variations in left ventricular ejection fraction (LVEF), and clinical laboratory parameters in all treated subjects.

Results

• From September 7, 2013 to January 30, 2015, they evaluated 149 candidates for eligibility and 148 were then randomly assigned to receive eltrombopag (n=74) and placebo (n=74).
• They matched the groups 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 × 10⁹/L [43.3]vs63.7 × 10⁹/L [48.0]), and poor-risk karyotype (16 [22%] of 74 cases in both groups).
• Febrile neutropenia (31 [42%] vs 28 [39%]), decreased white blood cell count (8 [11%] vs 5 [7%]), and hypophosphatemia (3 [4%] vs 9 [13%]) were the most common grade 3–4 adverse events (≥10% in either group).
• Serious adverse events occurred in 24 (32%) individuals in the eltrombopag group and 14 (20%) in the placebo group.
• They observed that 39 (53%) subjects in the eltrombopag group died vs 29 (41%) patients in the placebo group.
• They noticed similar thromboembolic events (5 [7%] vs4 [6%]) and mean (SD) change in LVEF (−2.5% [7.8] vs −4.3% [8.5]).