Claire Harrison, MD, DM, FRCP, FRCPath, of Guy’s and St Thomas’ NHS Foundation Trust, London, UK, discusses the MAJIC trial; the first randomized study comparing ruxolitinib to best available therapy in the UK for essential thrombocythemia (ISRCTN61925716). This is similar to studies that have been done in polycythemia vera (PV) and myelofibrosis, which looked at patients who were struggling with their current therapy, i.e. hydroxyethyl urea. Patients were randomized to receive either ruxolitinib or the best available therapy. Data presented at the EHA 2016 meeting demonstrated that the outcome with ruxolitinib is very similar to that with the best available therapy for controlling blood counts. Symptoms improved significantly in patients treated with ruxolitinib; however, there was also some increase in toxicity with regard to lowering of hemoglobin, anemia and infections. Data presented at the ASH meeting were analysed in more detail, looking at the occurrence of blood clotting, bleeding and transformation events. Further, Prof. Harrison highlights that they have performed next-generation sequencing (NGS) looking at allele burden and molecular responses, and correlating them to outcomes. The top-line data suggest that achieving molecular response doesn’t necessarily correlate with clinical response. However, it did correlate with aspects of symptom improvement. If a patient is anemic at the time of starting ruxolitinib, they are more likely to remain anemic or the anemia will get worse. Prof. Harrison also highlights that, although we know more about molecular responses now, we still need to do more research in order to understand the implications for disease management. Recorded at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA.