Thrombopoiesis‐stimulating agents and myelodysplastic syndromes

Abstract

SummaryThrombocytopenia in patients with myelodysplastic syndromes (MDS) is a frequent cause of haemorrhage-related morbidity and mortality, and is associated with increased risk of leukaemic transformation and reduced overall survival. In addition, thrombocytopenia in MDS limits the tolerability and therapeutic efficacy of disease-modifying therapies, such as azacitidine or lenalidomide. The recombinant human erythropoietin (rHuEPO) erythropoiesis-stimulating agents, epoetin and darbepoetin, are an established component of anaemia management in lower-risk MDS. Their success has, in turn, driven the development of haematopoietic growth factors targeting thrombocytopenia. While recombinant thrombopoietin (THPO) proved too immunogenic for clinical use, novel thrombopoiesis-stimulating agents (TSAs) have the potential to reduce bleeding events, decrease dependency on platelet transfusions and extend exposure to disease-modifying therapies. Two TSAs, eltrombopag and romiplostim, have demonstrated benefit in chronic immune thrombocytopenia purpura (ITP) and safety and efficacy data for use of these agents in MDS is growing. However, important safety concerns remain, such as the potential for stimulation of neoplastic myeloid clones by THPO agonists. In this narrative review, we discuss the rationale and biological mechanism for TSAs in MDS, describe the agents currently available and their mechanism of action, and present current clinical data relating to TSA safety and efficacy in the context of MDS.

Simultaneous Manifestation of Chronic Myelomonocytic Leukemia and Multiple Myeloma during Treatment by Prednisolone and Eltrombopag for Immune-Mediated Thrombocytopenic Purpura

“…Ineffective platelet production secondary to disordered maturation or proliferation of megakaryocytes has been considered as the other main mechanism of thrombocytopenia in MDS [25]. Eltrombopag has been shown to be useful to treat thrombocytopenia in MDS patients [26]. Platelet counts were improved or remained stable in 9 out of 12 cases, despite azacitidine treatment [27].…”

Human‐induced pluripotent stem cell‐derived blood products: state of the art and future directions

“…However, in contrast, other systems, such as micro carrier culture or 2D differentiation have shown a superior MK yield of between~30 and 6900 MK/iPSC [11,27,62]. For example, platelet stimulation by TPO or agonist to c-MPL (TPO receptor) are used in the clinic for some diseases to improve platelet counts (thrombocytopenias, myelodysplastic syndromes) [63,64]. Besides the method of differentiation, the composition of the differentiation mix (cytokines, small molecules) can also influence the efficiency of megakaryopoiesis.…”

Myelodysplastic Syndromes

“…67 One of the major shifts in clinical practice in the past few years is the increased use of thrombopoietin (TPO) receptor agonists in MDS. 68 Although romiplostim and eltrombopag are currently not approved for use in MDS, their label includes immune thrombocytopenia, which some patients with MDS also have. These agents can improve platelet counts and reduce bleeding events, especially in patients who have an endogenous TPO level less than 500 pg/mL and are not heavily dependent on platelet transfusions.…”