Polycythemia Vera: New Drug Treats Rare Blood Disorder

Lara C. Pullen, PhD

January 30, 2015

Ruxolitinib is superior to hydroxyurea in patients with an inadequate response to standard therapy, according to a newly published study. Ruxolitinib was able to control hematocrit, reduce spleen volume, and improve symptoms associated with polycythemia vera.

"It is very exciting to have new treatments in this space," Aaron Gerds, MD, from the Cleveland Clinic in Ohio, explained to Medscape Medical News. Dr Gerds was not affiliated with the study.

Alessandro M. Vannucchi, MD, from the University of Florence in Italy, and colleagues published the results of their phase 3 open-label study in the January 29 issue of the New England Journal of Medicine. The primary endpoint was both hematocrit control through week 32 and a reduction in spleen volume of at least 35% at week 32. The researchers considered patients with missing assessments to not have had a positive response.

The primary endpoint was achieved in 21% of patients in the ruxolitinib group vs 1% of patients in the standard therapy group (P < .001). Sixty percent of patients receiving ruxolitinib, and 20% of those receiving standard therapy, achieved hematocrit control. A reduction in spleen volume of at least 35% was achieved by 38% and 1% of patients in the two treatment groups, respectively. The majority (85%) of patients assigned to ruxolitinib continued to receive the drug for a median of 81 weeks. The study is ongoing, but not recruiting. The ruxolitinib group had 1.2 thromboembolic events per 100 patient years, which was fewer than expected in this high-risk population.

"Probably the most important part of this study was the improvement of symptoms," explained Dr Gerds. "The symptom relief was quite remarkable.... If you see a study on a new drug that makes patients feel better, it makes you very excited."

Although many patients with polycythemia vera respond to treatment with hydroxyurea, approximately 25% have an inadequate response or unacceptable adverse effects. Many of these patients continue to be treated with hydroxyurea despite their inadequate response or adverse effects.

Dr Gerds questioned whether the primary endpoint of hemocrit control would translate into a decrease in clot risk. "That is the burning, unanswered question," he emphasized.

The Cyto-PV trial found that a lower hematocrit can help lower the risk for cardiovascular death in patients with polycythemia vera, as reported by Medscape Medical News. The trial revealed that cytoreductions are important. What is not clear is whether or not risk for cardiovascular death is reduced regardless of the treatment used to lower hemocrit.

The European Medicines Agency has recommended this month that ruxolitinib be approved to treat polycythemia vera. Rituximab is an oral inhibitor of the Jak 1 and Jak 2 tyrosine kinases.

Dr Gerds cautioned against using ruxolitinib as frontline therapy until data are published about reduction of clot risk. Until then, the data point to a very exciting option for second-line therapy, he noted.

The study was supported by Incyte and Novartis. Five coauthors report receiving fees and/or other support from Novartis. Three coauthors report receiving personal fees from Incyte Corporation. Another coauthor reports receiving grant support and personal fees from Novartis and personal fees from Sanofi, Centers for Therapeutic Innovation, Shire, Gilead, YM Bioscience, and S Bio. Another coauthor reports receiving grant support and personal fees from Novartis and personal fees from Shire and AOP Orphan. Another coauthor reports receiving  grant support from Incyte Corporation, AstraZeneca, Lilly Oncology, Roche, Geron, NS Pharma, Bristol-Myers Squibb, Celgene, Infinity Pharmaceuticals, Gilead, Seattle Genetics, Promedior, Cell Therapeutics, Galena Biopharma, and Pfizer. The other authors and Dr Gerds have disclosed no relevant financial relationships.

N Engl J Med. Published online January 29, 2014 Abstract

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