Ruxolitinib: Another Option for Polycythemia Vera Patients with Poor RESPONSE

Patients with polycythemia vera who do not respond well to hydroxyurea may have another promising treatment option, according to results from the RESPONSE trial.

A recent phase 3 trial found that ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was superior to standard therapy in controlling hematocrit levels, reducing spleen volume, and improving polycythemia vera symptoms for patients who either had an inadequate response to hydroxyurea or had experienced unacceptable side effects.

These findings, which were published in The New England Journal of Medicine, could provide a treatment alternative for the approximately 25 percent of polycythemia vera patients who don’t respond well to hydroxyurea – the most commonly used cytoreductive drug used to treat the disease.

“This is the first time a drug has been evaluated in a controlled study specifically in this category of patients that have an advanced form of disease with dismal outcome,” Alessandro M. Vannucchi, MD, the study’s first author, told ASH Clinical News.

In the RESPONSE trial, investigators randomly assigned 222 adult patients with polycythemia vera to receive either ruxolitinib (n=110) or another single-agent therapy determined by their treating physician as the best available therapy (n=112). For the majority of patients, this was hydroxyurea (given to 58.9% of patients), followed by interferon (given to 11.6% of patients).

Patients in the ruxolitinib group received a starting dose of 10 mg twice daily. At week 32 of the study, researchers used MRI or CT scans to evaluate the proportion of patients who had both hematocrit control and a ≥35 percent reduction in spleen volume compared to baseline.

In the ruxolitinib group, 21 percent of patients achieved both hematocrit control and the reduction in spleen volume by week 32; however, only 1 percent of those in the standard therapy group had achieved both measures.

When the outcomes were looked at individually, investigators reported that significantly more patients in the ruxolitinib group achieved hematocrit control and were able to reduce spleen volume by at least 35 percent (p<0.001).

Complete hematologic remission was also more common in patients taking ruxolitinib (24%) compared to those on standard therapy (9%; p=0.003).

Patients taking ruxolitinib also reported fewer overall symptoms related to polycythemia vera, including itching, fatigue, and night sweats. After 32 weeks, 49 percent of patients taking ruxolitinib saw at least a >50 percent reduction in their symptom score (as measured by the Myeloproliferative Neoplasm Symptom Assessment Form) versus 5 percent of patients in the standard therapy group.

Nearly 85 percent of patients assigned to ruxolitinib continued to receive it at a median follow-up of 81 weeks, adding further support to its tolerability.

With the ongoing RESPONSE trial, Dr. Vannucchi said, investigators hope to learn more about how long ruxolitinib remains effective in controlling the disease. “Although ruxolitinib was very well-tolerated,” Dr. Vannucchi noted, “there was an apparent increase of non-melanoma skin cancers and an increase of herpes virus reactivation in the randomized phase. These events will be followed carefully over longer follow-up.”


Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372:426-35.