Targeted Therapy of Myelofibrosis

Background. Myelofibrosis (primary myelofibrosis, post-essential trombocythemia myelofibrosis, post-polycythemia myelofibrosis) is the most complex and pressing problem among all Ph-negative myeloproliferative diseases. The present article summarizes the author’s experience of using new Janus kinase inhibitors in routine clinical practice, and compares the data with the results of other clinical research. Aim. To evaluate the use of ruxolitinib in patients with myelofibrosis. Materials & Methods. Our analysis includes 48 patients (21 men and 27 women) with histologically verified myelofibrosis (primary myelofibrosis in 36 cases, post-essential trombocythemia myelofibrosis in 10 cases, and post-polycythemia myelofibrosis in 2 cases) in a chronic stage. All patients received ruxolitinib. Median age at the start of therapy was 60 years (range from 35 to 79). Massive splenomegaly (≥ 10 cm below the costal margin) was found in 34 (71 %) of 48 patients. The initial dose of ruxolitinib was determined by the platelet level. The efficacy of the therapy was evaluated in accordance with ELN 2013 criteria. Results. Median duration of treatment was 18 months (range from 1 to 50 months). Symptoms of intoxication were relieved in 33 of 37 patients (89 %). The spleen size decreased in 64 % of patients. In 33 % of cases spleen size did not change, whereas an increase was observed in 3 % of patients. In the majority of patients hemoglobin level remained stable through the course of treatment. Three of 14 transfusion dependent patients did not require blood transfusions after 3 months of therapy. In patients with high thrombocyte levels prior to ruxolitinib therapy the mean level was approaching normal by the end of the 1st month of treatment. The median JAK2V617F mutant allele burden at the beginning treatment was 56.5 % (n = 20; 22.5–126.1 %). After 6 moths of treatment it accounted for 62.3 % (n = 11; 25.4–79.7 %) and in 12 months accounted for 47.4 % (n = 12; 14.2–102.2 %). By the time of the analysis 42 of 48 patients continued the ruxolitinib treatment (88 %). Death occurred in 4 patients. Overall 1-year (92 %) and 2-year (87 %) survival corresponds to the data of COMFORT-I, COMFORT-II and JUMP clinical trials. Conclusion. Ruxolitinib showed to be an effective treatment for myelofibrosis. The most pronounced and rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. The tolerability of ruxolitinib was satisfactory in the majority of patients. According to the author’s data, ruxolitinib had a small impact on the JAK2V617F mutant allele burden. The overall survival rate in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was similar to that of in the clinical trials