The treatment options for myelofibrosis are very limited, with ruxolitinib the potent Janus kinase (JAK) 1 and 2 inhibitor, being the first and only drug approved specifically for this condition late last year. This study compared its efficacy and safety with the best available therapy for patients with myelofibrosis (Harrison C, et al. N Engl J Med. 2012;366:787-798). A total of 219 patients with primary myelofibrosis were randomized to therapy with ruxolitinib or to best available therapy. The primary end point was the proportion of patients reaching a ≥35% spleen volume reduction by week 48; the main secondary end point was the percentage of patients achieving this reduction by week 24. Imaging was used to assess spleen volume reduction.
At week 48, 28% of patients receiving the JAK inhibitor achieved at least a 35% reduction in spleen volume compared with 0% in the best available therapy cohort. At week 24, these percentages were 32% and 0%, respectively. The median palpable spleen length decreased by 56% at week 48 with JAK inhibition compared with a 4% increase in the best available therapy. The median duration of response has not yet been reached with ruxolitinib; 80% of patients in that group are still showing a response at 12-month follow-up.
Quality-of-life (QOL) measures were improved and the myelofibrosis-related symptoms were reduced in the ruxolitinib group compared with the other cohort. The most common grade ≥3 adverse events in each group were thrombocytopenia and anemia; 1 patient in each group discontinued treatment because of thrombocytopenia. Nonhematologic events were mild and rare; 2 cases of myeloid leukemia occurred in the best available therapy group. Although overall survival has not been documented yet with ruxolitinib therapy in this study, JAK inhibition in this patient population improves patients' QOL and significantly reduces disease symptoms. Additional studies are needed to investigate potential survival benefit and other safety and efficacy issues with this new drug therapy.
