DISCUSSION
bleeding, toxicity, AML, thrombocytopenia, MDS, cytopenic, deaths
CHRONIC MYELOMONOCYTIC LEUKEMIA, BLEEDING, DISEASE, THROMBOCYTOPENIA, AML, APLASTIC ANEMIA
The occurrence of severe thrombocytopenia in patients with low-risk MDS still represents a challenging condition because of the important burden of related AEs and the lack of effective treatments. In most countries, only PLT transfusions are currently offered to prevent or treat bleeding in these subjects. Despite this unmet clinical need, few investigational products have been tested. Among them, TPO mimetics are the most attractive: however, though the use of romiplostim seemed promising in a randomized trial,Preliminary results of this trial already showed high rates of PLT-R in this challenging subset of patients.Importantly, the findings from the present trial show a favorable safety profile in terms of long-term AEs and AML evolution/disease progression.While the rate of PLT-R was confirmed, a complete PLT-R (27.9%) was observed in the eltrombopag arm only. Occurrence of a small fraction of PLT-R in the placebo arm was probably because of the spontaneous variability of hematologic parameters in patients with MDS during the course of the disease, as predetermined by the sample size calculation and as commonly observed also in other randomized studies in patients with low-risk MDS.Our findings also corroborate with results from a recent multicenter retrospective study performed in France to evaluate the use of eltrombopag in patients with MDS (N = 50) and chronic myelomonocytic leukemia (N = 11).The dose of eltrombopag (50 mg once daily) to obtain PLT-R was the same as that used in our trial but we observed a substantially shorter median time to reach PLT-R (2.1 Similar to what is observed in aplastic anemia, a sizable fraction of patients receiving eltrombopag also achieved an erythroid/granulocytic response. This particular finding deserves further evaluation in larger cohorts of cytopenic patients with low-risk MDS.As expected, patients in the eltrombopag arm had a higher rate of nonhematologic AEs and 18 patients necessitated permanent treatment discontinuation because of persistent drug-related AEs. Most grade 3-4 AEs occurred early during treatment, within the first 24 weeks, and were reversible upon drug discontinuation. However, no differences were reported between the two arms for deaths.The most important safety evaluation, however, concerned the risk of the increase in blasts and MDS progression/AML evolution, which was shown during romiplostim treatment in a similar trial.Finally, it should be stressed that a relatively low daily dose of eltrombopag (50 mg once daily) was identified as the optimal dose at which patients more commonly achieved a consistent PLT-R, a finding also confirmed in the real-life setting,In conclusion, eltrombopag has an acceptable toxicity profile and is effective in raising and maintaining PLT count and reducing bleeding without any associated risk of MDS progression.