STOCKHOLM – Continuous ruxolitinib therapy extends survival over that seen with best available therapy (BAT) in patients with myelofibrosis and also provides durable reductions in splenomegaly, according to results released at the 18th Congress of the European Hematology Association (EHA).
The data, from a three-year follow-up of the phase 3 Myelofibrosis Study with Oral JAK Inhibitor Treatment II (COMFORT-II) study, also show that the agent continues to be well tolerated with prolonged treatment.
Ruxolitinib is a potent and selective inhibitor of Janus kinase (JAK)1 and JAK2 that is approved for the treatment of intermediate- and high-risk myelofibrosis.
Alessandro Vannucchi, MD, associate professor of hematology at the University of Florence, Italy, presented three-year follow-up data in study participants.
A total of 219 patients with intermediate-2 or high-risk mylofibrosis were randomized in a 2:1 ratio to receive ruxolitinib (15 or 20 mg bid, based on baseline platelet count [100-200 or >200×109/L, respectively]), or BAT.
Best available therapy included any commercially available agents (as monotherapy or in combination) or no therapy at all and which could be changed during the treatment phase.
The analysis showed a 52% reduction in mortality risk in the ruxolitinib cohort versus BAT (hazard ratio = 0.48, 95% CI, 0.28-0.85, P=0.009). The estimated probability of survival at 144 weeks was significantly higher with ruxolitinib than with BAT (81% versus 61%, respectively).
Overall, 51.4% of ruxolitinib-treated patients achieved a ≥35% reduction from baseline in spleen volume. The median spleen response has not beet been reached.
Ruxolitinib treatment remained well tolerated with long-term use.
Myelofibrosis is characterized by marrow fibrosis, progressive anemia, and extramedullary hematopoiesis, manifested mainly as splenomegaly. Except for allogeneic stem-cell transplantation, treatment is palliative and does not address the characteristic abnormality identified in myelofibrosis, which is a dysregulation of Janus kinase (JAK)-mediated cytokine and growth-factor signal transduction. Patients with myelofibrosis have a median overall survival of 5.7 years.
Dr. Vannucchi said that the findings are important because ruxolitinib is the first drug that has been shown to improve overall survival in advanced myelofibrosis.
Elsewhere at the meeting, investigators reported that long-term treatment with ruxolitinib may stabilize or reverse bone marrow fibrosis. Bone marrow fibrosis is a key marker of progressive disease in patients with myelofibrosis
Written by Jill Stain
Jill Stein is a Paris-based freelance medical writer.