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Ruxolitinib for the Treatment of Essential Thrombocythemia.
HemaSphere. 2018 August
Deregulated Janus Kinase 2 (JAK2) activation is central to the pathogenesis of most myeloproliferative neoplasms (MPNs), of which essential thrombocythemia (ET) is the most common entity. Patients with ET are risk-stratified according to their risk of thrombo-hemorrhagic complications. High-risk patients are offered treatments to reduce their platelet count using cytoreductive therapy. The disease course is often long and therapy intolerance is not infrequent. Ruxolitinib, a Janus Kinase (JAK) 1/JAK2 inhibitor, has demonstrated efficacy in patients with both myelofibrosis (MF) and polycythemia vera and is well tolerated. Side effects include predictable cytopenias and an augmented risk of infections. Ruxolitinib has been investigated in a small group of ET patients who were refractory/intolerant to hydroxycarbamide (HC) and demonstrated improvements in both symptoms and splenomegaly. Of note, a proportion of treated patients (13.2%) also had a significant reduction in platelet counts. However, these results require further validation in comparison with conventional therapy. Recently, a randomized-controlled phase 2 study (MAJIC-ET) assessed the role of Ruxolitinib in patients refractory or intolerant to HC. This study revealed that Ruxolitinib demonstrated some clinical efficacy but was only superior in terms of symptom control. In clinical practice, some individuals with ET do exhaust all potential treatment options and there may well be a role for Ruxolitinib in such patients or those with a significant symptom burden. However, in the wider context the goal of therapy with the use of JAK inhibitor therapy in ET needs to be defined carefully and we explore this within this timely review article.
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