Abstract
INTRODUCTION: Ruxolitinib was the first JAK2 inhibitor approved for the treatment of primary and secondary myelofibrosis. It is currently used worldwide as first-line therapy for advanced disease (intermediate-2 and high-risk) and is effective in polycythaemia vera (PV) and essential thrombocythaemia (ET), but not funded for this indication in many countries. Ruxolitinib has proven benefits with respect to symptom control, reduction in spleen size and prolongation of survival; however, it rarely induces a substantial reduction in allele burden and never provides a cure. Moreover, there are frequently encountered adverse effects and dosing issues that require careful management to optimise its therapeutic benefit. METHODS AND RESULTS: In this case-based review, we use seven informative common clinical scenarios to discuss appropriate investigation and management of cytopenias and infection issues. CONCLUSIONS: We make recommendations based on 15 years of experience in using ruxolitinib and other JAK inhibitors for the treatment of myelofibrosis. We discuss when allogeneic haematopoietic stem cell transplantation (AHSCT) should be considered and some of the currently available alternative JAK inhibitors and trial options when AHSCT is not an option.