Thrombopoietin receptor agonists : present and future Volume 12, issue 5, Septembre-Octobre 2006


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Centre de référence sur les cytopénies auto-immunes, service de médecine interne, hôpital Henri Mondor, 51 Av. du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex

More than 10 years after the cloning of thrombopoietin (Tpo), platelet transfusions are still the only way to manage myeloablative chemotherapy-induced thrombocytopenias. The initial development of recombinant Tpo has been disappointing since its clinical efficacy was not demonstrated in the most critical situations and some cases of severe thrombocytopenias induced by neutralizing antibodies crossreacting with endogenous Tpo had been reported. More recently, some Tpo-receptor agonists or « Tpo mimetic agents » have been developed by pharmaceutical companies and two of them, AMG 531 and eltrombopag have entered into clinical phase II/III studies. Preliminary studies, mainly performed in patients with immune thrombocytopenic purpura (ITP), have shown a promising 80-85 % response rate with a relatively good short-term safety profile. Ongoing and future studies will be helpful to answer the following questions : 1) What could be the place of Tpo-R agonists in the treatment of ITP and 2) Will these molecules show a good efficacy/safety ratio for the management of the most critical situations in hematology such as myelodysplasia-associated or chemotherapy-induced chronic thrombocytopenias.