A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome (MDS) receiving decitabine.

Leukemia & lymphoma (Impact Factor: 2.61). 08/2012; 54(2). DOI: 10.3109/10428194.2012.713477
Source: PubMed

ABSTRACT Abstract MDS patients receiving hypomethylating agents commonly develop thrombocytopenia. This double-blind study evaluated the efficacy and safety of romiplostim, a peptibody protein that increases platelets, in MDS patients receiving decitabine. Patients received romiplostim 750μg (n=15) or placebo (n=14) and decitabine. Median platelet counts at the beginning of each decitabine cycle trended lower in placebo treated than romiplostim treated patients. Bleeding events occurred in 43% of placebo and 27% of romiplostim patients; platelet transfusions were administered to 57% of placebo and 47% of romiplostim patients. Overall clinical therapeutic response was achieved by 21% of placebo and 33% of romiplostim patients. Treatment was generally well tolerated. Progression to AML occurred in one patient per group. Adding romiplostim to decitabine treatment is well tolerated and may be beneficial, as indicated by trends toward higher platelet counts at the beginning of each treatment cycle and lower platelet transfusion rates and percentages of patients with bleeding events.

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    Leukemia Research 09/2014; · 2.69 Impact Factor
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    ABSTRACT: Thrombocytopenia is common (40–65%) and potentially serious in myelodysplastic syndromes (MDS). A systematic review was conducted to determine the safety and efficacy of adding a thrombopoietin-receptor (THPO-R) agonist to standard MDS treatment. MEDLINE, EMBASE and CENTRAL databases were searched. We included randomized controlled trials comparing a THPO-R agonist to placebo. A meta-analysis of the effects was performed. Endpoints included bleeding and platelet transfusion rates, risk of progression to acute myeloid leukaemia (AML) and mortality. Three hundred and eighty four patients from five trials were included, four using romiplostim and one using eltrombopag. Overall, the relative risk (RR) of bleeding with romiplostim versus placebo was 0·84 [95% confidence interval (CI): 0·57–1·24]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate (RR 0·92; 95% CI: 0·86–0·99), as well as the exposure-adjusted platelet transfusion rate (RR 0·69; 95% CI: 0·53–0·88). The RR of AML progression with romiplostim was 1·36 (95% CI: 0·54–3·40), however the outcome data were judged as higher risk of bias. Romiplostim is promising in its ability to decrease patient-important outcomes: bleeding and platelet transfusion need. Although the risk of AML progression was not increased, due to unclear risk of bias in the data, this safety concern is difficult to assess. Therefore, romiplostim cannot yet be routinely recommended. Early eltrombopag data is promising.
    British Journal of Haematology 08/2014; · 4.94 Impact Factor
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    ABSTRACT: The two main blood components commonly transfused to patients with hematologic malignancies are red cells and platelets. A number of randomized-controlled trials (RCTs) have been conducted to inform safe and effective use of platelets. The ready availability of platelet concentrates has undoubtedly made a major contribution to the supportive management of thrombocytopenic bleeding. But the optimal use of prophylactic platelet transfusions for the prevention of hemorrhage remains controversial. Two RCTs of prophylactic platelet transfusions have recently been completed in adults with thrombocytopenia due to hematologic malignancies or their treatment. Both found a no-prophylaxis approach led to higher rates of World Health Organization (WHO) grade 2-4 bleeding overall. There is ongoing discussion about whether the effectiveness of prophylactic platelet transfusions may differ between sub-groups of patients with hematologic malignancies, and whether a no-prophylaxis approach is non-inferior to prophylactic platelet transfusions in autologous hematopoietic stem cell transplantation. In contrast to use of platelets, there is very little evidence available to direct optimal use of red cells in patients with hematologic malignancies. Many patients with myelodysplasia will become red blood cell transfusion-dependent during the course of the disease, but few data exist to inform the optimal transfusion threshold and target hemoglobin concentration that translate into a significantly improved quality of life for these patients. Learning goals At the conclusion of this activity, participants should be aware that: - recent trials have started to address fundamental issues of effectiveness for use of a blood component (platelets) by comparison to a no-transfusion policy for inpatients receiving therapy for hematologic malignancies; - the results of 2 recent randomized trials have indicated that prophylactic platelet transfusions overall reduced bleeding rates in patients; - there is evidence that the effectiveness of prophylactic platelet transfusions may differ between sub-groups of patients with hematologic malignancies. Further research is necessary to establish whether a no-prophylaxis approach is non-inferior to prophylactic platelet transfusions in patients receiving autologous hematopoietic stem cell transplants, and whether prophylactic platelet transfusions are a (cost)-effective use of resources in these patients, and how these findings might relate to outpatients with chronic thrombocytopenia; - there is minimal evidence for the optimal use of red cells for inpatients with hematologic malignancies; - information is required on a range of key clinical outcomes, including health related quality of life (HrQoL). It is unclear whether higher hemoglobin concentration thresholds for red cell transfusion in patients with myelodysplasia might improve HrQoL.
    Hematology Education: the education program for the annual congress of the European Hematology Association. 06/2014; 8:421-426.