Eltrombopag plus cyclosporine A for moderate aplastic anemia (EMAA): a placebo-controlled, double-blind, phase 3 trial.

Eltrombopag combined with horse antithymocyte globulin and cyclosporine A (CSA) is the standard of care for patients with severe aplastic anemia who are not eligible for stem cell transplantation. No consensus exists on the optimal treatment of moderate aplastic anemia (MAA). The "Eltrombopag for MAA" (EMAA) trial is an investigator-initiated, prospective, randomized, placebo-controlled, double-blind, multicenter, phase III trial and compared eltrombopag+CSA (n=41) with placebo+CSA (n=44) as a first-line therapy for MAA patients with clinically significant cytopenia. In patients with evaluable response at week 24 (n=75), the overall response rate (ORR), including partial response (PR) and complete response (CR), was significantly higher in the eltrombopag+CSA arm (71.4%; 95% confidence interval [CI], 54.8%-83.8%) than in the placebo+CSA arm (42.5%; 95% CI, 28.5%-57.8%) (p=0.011, Fisher's exact test; primary endpoint). After response assessment at week 24 and unblinding, patients in the placebo arm without CR were switched to receive eltrombopag in addition to continued CSA. This group achieved an ORR of 73.5% by week 48 (p=0.009, McNemar test, comparing response at 24 vs. 48 weeks). Relapse rate and failure-free survival did not differ significantly among the arms. Eltrombopag was well tolerated without new safety concerns. Adding eltrombopag to CSA for first-line treatment of MAA significantly improves trilineage hematologic response at week 24 and addition of eltrombopag in patients without CR after 24 weeks of single-agent CSA treatment also significantly improves the ORR. The trial was registered at www.clinicaltrials.gov as #NCT02773225 and at European Union Drug Regulating Authorities Clincial Trials as EudraCT2014-000174-19.