Optimising the Use of Ruxolitinib in Inadequately Controlled Polycythaemia Vera

P olycythaemia vera (PV) is an uncommon chronic myeloproliferative neoplasm characterised by increased red-cell mass. The condition is currently managed by phlebotomy and/or palliative cytoreductive therapy, most commonly using hydroxyurea (HU). However, around 25% of patients have an inadequate response and/or unacceptable adverse effects; furthermore, patients with resistance to HU appear to have shorter survival than other patients with PV. Recently, a second-line treatment has become available. Ruxolitinib, an oral inhibitor of the Janus kinase (JAK) 1 and JAK 2 tyrosine kinases, has recently received regulatory approval for the treatment of patients with PV who are resistant to or intolerant of HU. This treatment offers the potential to significantly reduce phlebotomy requirements and improve the symptom burden. However, in order to determine which patients will benefit most from ruxolitinib, it is necessary to identify those who are inadequate responders to HU, a definition that is not currently consensual in the literature. Five patient groups, for whom ruxolitinib may be a beneficial second-line treatment option, have been proposed. These comprise patients who are at high risk and retain a high symptom burden after HU, require frequent phlebotomy, have an elevated leukocyte count, are intolerant to HU or interferon, or have palpable splenomegaly.