Ruxolitinib Continues to Impress in Long-Term Myelofibrosis Follow-Up

Beth Fand Incollingo @fandincollingo
Published: Saturday, Dec 05, 2015

Dr. Claire Harrison

Claire Harrison, MD

Ruxolitinib (Jakafi), a drug approved in 2011 to reduce the volume of enlarged spleens in patients with myelofibrosis, continues to work in this population when taken long-term.

Data showing that spleen size reduction and overall survival (OS) improvements were maintained in patients with advanced myelofibrosis who took the targeted drug over 5 years were shared when final results of the COMFORT-II study—one of the clinical trials that led to ruxolitinib’s approval—were presented during the 57th Annual Meeting of the American Society of Hematology.

In the earlier COMFORT-II findings that led to the therapy’s approval, published in 2012, ruxolitinib significantly decreased spleen size in 28% of patients, but no decrease was seen in patients in the control arm, who were taking best available therapy (BAT).

In the longer-term study, ruxolitinib reduced splenomegaly at any time during treatment by at least 35% in 53.4% of enrolled patients. Of those who crossed over to the ruxolitinib arm from the BAT group, which primarily took hydroxyurea, 42.2% experienced a significant reduction in splenomegaly.

The 5-year results also showed that the drug’s safety and tolerability profiles did not change over time, noted Claire Harrison, MD, a professor of hematology at Guy’s and St. Thomas’ NHS Foundation Trust in London, who presented the findings. Importantly, Harrison said, an OS benefit with the drug that was demonstrated after 3 years of study was also maintained, and would have reflected a more striking improvement had crossover by patients from the BAT arm to the ruxolitinib arm not confounded those results.

Ruxolitinib is an oral JAK1 and JAK2 inhibitor that slows or halts the cell-signaling process that causes myelofibrosis, a disease characterized by the replacement of healthy bone marrow with scar tissue. The spleen becomes enlarged when, in the absence of bone marrow, it takes over part of the job of producing new blood cells. Myelofibrosis can also bring on anemia, night sweats, and muscle and bone pain—as well as a reduction in life expectancy.

Harrison said that ruxolitinib, a tyrosine kinase inhibitor that is also approved to treat the rare blood disorder polycythemia vera, has made an enormous difference in the lives of tens of thousands of patients with myelofibrosis and has been “a great joy” to prescribe.

“For the first time, I was able to treat patients with a drug that made them feel better,” Harrison said of ruxolitinib. “A week or so later, they were smiling, and one patient was crying because he was able to take a bath for the first time in 5 years, because the disease causes dramatic water-induced pruritis (itching). These patients gained weight, were sleeping better, and were physically performing better. They’re able to enjoy life. They said, ‘I took a walk, I played golf, I went out with my wife, I didn’t feel a burden on my family anymore, I was able to work.’ There are patients I see now who’ve been on the study for 5 years who say, ‘I know I’m alive because of this drug.’”

Harrison noted that COMFORT-II provides a large amount of data for a population with a rare condition. Initially, 146 patients were randomized to ruxolitinib and 73 to BAT. Patients stayed on the study until they experienced progressive splenomegaly. In the ruxolitinib arm, 39 patients completed 5 years of follow-up; 11 in the BAT arm crossed over and also completed 5 years of treatment, with another 28 from the BAT arm dropping out.

The study found that the median duration of response for a significant reduction in spleen volume was 3.2 years, but Harrison said there was “a really strong suggestion of a plateau in response after that,” meaning that, for patients who stayed on the medication after hitting the 3.2-year mark, “there was hardly any dropoff” in control of their spleen size in the 2 years that followed.

She added that 32% of patients taking ruxolitinib experienced stabilization of fibrosis, and that nearly 16% saw an improvement in that area, including 4 patients who dropped down to a normal amount of fibrosis in their marrow. In 18.5% of patients, however, fibrosis worsened.

After a drop in the first 12 weeks, hemoglobin levels recovered to match those in the BAT arm and then stayed stable, which Harrison described as “very reassuring for patients and clinicians.” Reductions in JAK2 V617F allele burden, a speculative biological endpoint that may factor into research, were apparent with longer-term treatment.

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