The role of AMG-531 in the treatment of thrombocytopenia in idiopathic thrombocytopenic purpura and myelodysplastic syndromes.
Thrombocytopenia can be seen in a variety of disease states, including immune mediated thrombocytopenic purpura (ITP) and myelodysplastic syndromes (MDS). The most concerning complication is the development of hemorrhagic complications that may contribute to patient morbidity and mortality. The ligand thrombopoeitin (TPO) and its interaction with its receptor (c-mpl) are important in platelet production. Thrombopoietic agonists can help in the management of thrombocytopenia related to these conditions. Amgen Megakaryopoiesis Protein 531 (AMG-531) (Romiplostim) is a recombinant TPO with a peptide fragment that shares no sequence homology with endogenous TPO, preventing the production of neutralizing antibodies. Recent studies have shown that it is effective in raising platelet counts, and is well tolerated in ITP and MDS patients. In this review, we discuss thrombopoiesis regulation by TPO; the chemistry, pharmacokinetics and pharmacodynamics of AMG-531 in animals and humans; the pathophysiological mechanisms leading to thrombocytopenia in ITP and MDS; and clinical trials demonstrating its efficacy in treating thrombocytopenia.
Cleveland Clinic Taussig Cancer Center, Department of Hematologic Oncology and Blood Disorders, 9500 Euclid Avenue R35, Cleveland, Ohio 44195, USA.
Ramon V
RV
Tiu
Mikkael A
MA
Sekeres
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007262:Infusions, Intravenous; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000628:therapy*; D011961:Receptors, Fc / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000737:chemistry; D013921:Thrombocytopenia / Q000628:therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*; D016896:Treatment Outcome
D002352:Carrier Proteins; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim