Thrombocytopenia is made worse when myelodysplastic syndromes with high risk are treated with azacitidine. Therefore, Eltrombopag and azacitidine were studied using a 3 + 3 cohort design.

Eltrombopag dosages ranging from 25 to 300 mg were given to patients with baseline platelet counts under <150×109/l. After an 8-day eltrombopag pre-phase, 2 cycles of combination treatment were administered. There were no dose-limiting effects among the 31 individuals. 300 mg was the maximum tolerated dosage (MTD).

On day 8, there were sometimes brief elevations in bone marrow blasts, but no patient had undergone a protocol-defined progression after receiving eltrombopag monotherapy. After 3 and 6 therapy cycles, the marrow response rates were 32% and 29%, respectively. After cycle two, a modified International Working Group 2006 platelet response was attained by 70% of patients treated below and 36% of those treated at the MTD. In the first two cycles of therapy, 67% of the platelet transfusion-independent patients treated at the MTD developed transfusion dependence. Apart from the absence of disease progression, the results were consistent with a Phase III trial that was previously published (A Study of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]).

Eltrombopag/azacitidine is safe according to traditional standards determined by adverse-event reporting. Further combination trials in high-risk diseases should be carefully examined in light of SUPPORT and our own descriptive effectiveness findings.