research paper
Safety and efficacy of thrombopoietin-receptor agonists in myelodysplastic syndromes: a systematic review and meta-analysis of randomized controlled trials
Anca Prica,1 Michelle Sholzberg2 and Rena Buckstein3 1
Division of Medical Oncology and Haematology,
Princess Margaret Cancer Centre/Mount Sinai Hospital, University of Toronto,
2
Division of
Haematology, St. Michael’s Hospital, University of Toronto, and 3Division of Medical Oncology and Haematology, Odette Cancer Centre/ Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada Received 10 April 2014; accepted for publication 2 July 2014 Correspondence: Dr. Anca Prica, Medical Oncology and Haematology, Princess Margaret Cancer Centre, 5-303B, Toronto M5G 2M9, ON, Canada. E-mail: [email protected]
Summary 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 084 [95% confidence interval (CI): 057–124]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate (RR 092; 95% CI: 086–099), as well as the exposure-adjusted platelet transfusion rate (RR 069; 95% CI: 053–088). The RR of AML progression with romiplostim was 136 (95% CI: 054–340), 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. Keywords: thrombopoietin, thrombopoiesis, thrombopoietin-receptor agonist, myelodysplastic syndromes .
Myelodysplastic syndromes (MDS) are heterogeneous malignant myeloid stem cell disorders in adults with a median age of onset of 72 years. These haematological malignancies may affect as many as one in 1000 Canadians over the age of 65 years (Buckstein et al, 2007). MDS is characterized by ineffective haematopoiesis and peripheral blood cytopenias. While the development of acute myeloid leukaemia (AML) may occur, 75% of patients die prematurely from causes other than leukaemia. Thrombocytopenia, defined as a platelet count of
Safety and efficacy of thrombopoietin-receptor agonists in myelodysplastic syndromes: a systematic review and meta-analysis of randomized controlled trials
Anca Prica,1 Michelle Sholzberg2 and Rena Buckstein3 1
Division of Medical Oncology and Haematology,
Princess Margaret Cancer Centre/Mount Sinai Hospital, University of Toronto,
2
Division of
Haematology, St. Michael’s Hospital, University of Toronto, and 3Division of Medical Oncology and Haematology, Odette Cancer Centre/ Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada Received 10 April 2014; accepted for publication 2 July 2014 Correspondence: Dr. Anca Prica, Medical Oncology and Haematology, Princess Margaret Cancer Centre, 5-303B, Toronto M5G 2M9, ON, Canada. E-mail: [email protected]
Summary 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 084 [95% confidence interval (CI): 057–124]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate (RR 092; 95% CI: 086–099), as well as the exposure-adjusted platelet transfusion rate (RR 069; 95% CI: 053–088). The RR of AML progression with romiplostim was 136 (95% CI: 054–340), 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. Keywords: thrombopoietin, thrombopoiesis, thrombopoietin-receptor agonist, myelodysplastic syndromes .
Myelodysplastic syndromes (MDS) are heterogeneous malignant myeloid stem cell disorders in adults with a median age of onset of 72 years. These haematological malignancies may affect as many as one in 1000 Canadians over the age of 65 years (Buckstein et al, 2007). MDS is characterized by ineffective haematopoiesis and peripheral blood cytopenias. While the development of acute myeloid leukaemia (AML) may occur, 75% of patients die prematurely from causes other than leukaemia. Thrombocytopenia, defined as a platelet count of
