Long-term follow-up of a phase 3 study comparing ruxolitinib with best available therapy in patients with polycythemia vera (PV) resistant to or intolerant of treatment with hydroxyurea revealed that complete hematologic remission was maintained at 256 weeks for approximately half of those who achieved this study endpoint at 32 weeks following initiation of ruxolitinib. The findings from this study were published in Lancet Haematology.1

Polycythemia vera, a myeloproliferative neoplasm (MPN), is characterized by an increase in red blood cell mass, with elevated levels of white blood cells and platelets also observed in a substantial proportion of patients with this disease. Most patients with PV have disease characterized by JAK2 mutations.

The main goals of treatment in PV are to reduce the symptom burden, as well as the risks of a thromboembolic event and disease transformation to myelofibrosis or acute myeloid leukemia. Standard first-line therapy options for patients with high-risk PV are typically hydroxyurea or interferon alfa. However, approximately 25% of these patients will require an alternative treatment approach due to disease resistance, symptom persistence, or an inability to tolerate these therapies.

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In this randomized, open-label clinical trial (RESPONSE; ClinicalTrials.gov Identifier: NCT01243944), 222 patients with PV previously treated with hydoxyurea were randomly assigned in a 1:1 ratio to receive either ruxolitinib, a JAK1 and JAK2 inhibitor, or best available therapy (ie, hydroxyurea, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or observation without pharmacological treatment). The primary composite study endpoint was the proportion of patients achieving both hematologic control without phlebotomy and a reduction of at least 35% in spleen size from baseline at 32 weeks of treatment. Complete hematologic remission at week 32, defined according to prespecified criteria for hematocrit level, and white blood cell and platelet counts, was a secondary endpoint of the study.

Previously published results of the primary analysis of the RESPONSE trial showed that the primary study endpoint was met for 21% of patients treated with ruxolitinib vs 1% of those receiving best available therapy (P =.001).2 In addition, 24% of patients treated with ruxolitinib compared with 9% receiving best available therapy had achieved a complete hematologic remission (P =.003). Grade 3 or 4 anemia occurred in 2% and 0% of patients enrolled in the ruxolitinib and best available therapy arms, respectively, and grade 3 or 4 thrombocytopenia occurred in 5% of patients treated with ruxolitinib and 4% of patients receiving best available therapy. Through week 32, 1 and 6 patients treated with ruxolitinib and best available therapy, respectively, experienced a thromboembolic event.2

In this long-term analysis of the RESPONSE study completed after 5 years of follow-up, the primary composite response and hematologic complete remission were maintained at 256 weeks from initiation of treatment in 74% and 55% of patients who had achieved these respective endpoints at 32 weeks in the primary analysis.

In the intention-to-treat analysis, which did not account for crossover, rates of 5-year OS were 91.9% and 91.0% for those treated with ruxolitinib and best available therapy, respectively. No new safety signals were observed on long-term follow-up, although 2 on-treatment deaths occurred in the group receiving ruxolitinib, with 1 death, due to gastric adenocarcinoma, attributed to the study drug.   

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The 2019 approval of ruxolitinib by the US Food and Drug Administration (FDA) for the treatment of patients with hydroxyurea-pretreated PV was supported by the results of the RESPONSE study.3

“We showed that ruxolitinib is a safe and effective long-term treatment option for patients with [PV] who are resistant to or intolerant of hydroxyurea,” the study authors commented in their concluding remarks. “Taken together, ruxolitinib treatment offers the first widely approved therapeutic alternative for this post-hydroxyurea patient population.”


1. Kiladjian JJ, Zachee P, Hino M, et al. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study [published online January 23, 2020]. Lancet Haematol. doi: 10.1016/S2352-3026(19)30207-8

2. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(17):1670-1671. 3. Ruxolitinib [package insert]. Wilmington, DE: Incyte Corporation; 2020.