ATLANTA – Ruxolitinib reduces splenomegaly and other symptoms commonly associated with myelofibrosis, and the results are maintained for at least two years, according to results released at the 54th American Society of Hematology Annual Meeting.

The findings are drawn from a median follow-up of 112 weeks in patients who were randomized in a 2:1 ratio to receive either oral ruxolitinib or best available therapy (BAT) as part of the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment II (COMFORT-II) study. Ruxolitinib is a Janus kinase inhibitor with selectivity for subtypes 1 and 2 of this enzyme.

The phase III study also found that the medication was associated with an improvement in overall survival (OS).

Francisco Cervantes, MD, associate professor of hematology at the University of Barcelona, presented results in 107 of 146 ruxolitinib-treated and 45 of 73 BAT-treated patients who entered the extension phase of the study after completing 24 weeks of treatment. Best available therapy was defined as any commercially available agent given as monotherapy or in combination or no therapy at all.

Study participants had intermediate-2 or high risk myelofibrosis and splenomegaly at enrollment. All patients had disease that was refractory to available therapies, had side effects requiring their discontinuation, or were ineligible for available therapies and had disease requiring treatment.

Myelofibrosis is a bone marrow disorder characterized by splenomegaly, anemia, and debilitating symptoms (for example, fatigue, weakness, night sweats, pruritus, bone and muscle pain, and weight loss) that impair routine activities and reduce quality of life. Historically, treatments have been largely palliative.

Research has shown that dysregulated JAK-signal transducer and activation of transcription (STAT) signaling is associated with the pathologic myelofibrosis state. The JAK inhibitors have been developed to abrogate this pathologic signaling pathway.

At follow-up, 70 (48.3%) patients receiving the JAK 1 &2 inhibitor achieved a ≥35% reduction from baseline in spleen volume at any time during the study. Most reductions were sustained with ongoing treatment over two years.

Also, 132 of 136 patients who had post-baseline assessments, or 97.1%, experienced clinical benefit with at least some reduction in spleen volume.

Ongoing ruloxitinib therapy was associated with sustained reductions in spleen ≥35%; the probabilities of maintaining the spleen response was 75% at week 48 (95% CI, 61%-84%) and 58% at week 84 (95% CI, 35%-76%).

In an intent-to-treat analysis, patients in the ruxolitinib cohort had superior survival to patients in the BAT cohort (HR=0.51; 95% CI, 0.26-0.99 P=0.041).

The toxic effects of the drug were usually managed with dosage adjustments.

By Jill Stein
Jill Stein is a Paris-based freelance medical writer.