Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia.
BACKGROUND
Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1-risk MDS.


METHODS
Patients who had thrombocytopenia with low-risk/intermediate-1-risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks.


RESULTS
The primary endpoint- the number of clinically significant bleeding events (CSBEs) per patient-had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 10(9) /L (P < .0001). For patients who had baseline platelet counts <20 × 10(9) /L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar.


CONCLUSIONS
Romiplostim treatment in patients with low-risk/intermediate-1-risk MDS increased platelet counts and decreased the number of bleeding events and platelet transfusions. Although study drug was discontinued because of an initial concern of AML risk, survival and AML rates were similar with romiplostim and placebo.
Clinic for Oncology, Hematology, and Palliative Medicine, Marien Hospital Dusseldorf, Dusseldorf, Germany.
Aristoteles
A
Giagounidis
Ghulam J
GJ
Mufti
Pierre
P
Fenaux
Mikkael A
MA
Sekeres
Jeffrey
J
Szer
Uwe
U
Platzbecker
Andrea
A
Kuendgen
Gianluca
G
Gaidano
Wieslaw
W
Wiktor-Jedrzejczak
Kuolung
K
Hu
Paul
P
Woodard
Allen S
AS
Yang
Hagop M
HM
Kantarjian
D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010919:Placebos; D011961:Receptors, Fc / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000473:pathology; D013926:Thrombopoietin / Q000627:therapeutic use*; D016896:Treatment Outcome
D010919:Placebos; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim
drug therapy; myelodysplastic syndromes; randomized controlled trial; romiplostim; thrombocytopenia