Among patients with treatment-resistant polycythemia vera (PV) intolerant to hydroxycarbamide (HC-INT/RES), ruxolitinib appears to improve clinical outcomes compared with best available therapy (BAT), according to research published in the Journal of Clinical Oncology.

JAK2 mutations are typically implicated in PV, with constitutively active JAK-STAT signaling. Although HC is typically used in the first line, some patients develop treatment resistance; these patients generally have poor outcomes, and new treatments are consequently needed.

Previous research has suggested that ruxolitinib may control blood counts and improve symptoms among patients with high-risk PV. For the randomized phase 2 MAJIC-PV study, researchers evaluated whether ruxolitinib improves outcomes compared with BAT among patients with HC-INT/RES PV.

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Overall, 180 patients were enrolled, of whom 87 were randomly assigned to receive BAT and 93 were assigned to receive ruxolitinib. In the study cohort, the median age was 66 years, 58% of patients were male sex, the median number of prior therapy lines was 1, and 97% of patients had a JAK2V617F mutation.

Analysis showed that 43% of patients in the ruxolitinib arm and 26% of patients in the BAT arm had a complete response (odds ratio, 2.12; P =.02). Furthermore, patients who received ruxolitinib had a longer duration of complete response (hazard ratio [HR], 0.38; P <.001).

Both patients who, overall, reached a complete response within 1 year of treatment initiation (HR, 0.41; P =.01) and patients in the ruxolitinib group (HR, 0.58; P = .03) had better event-free survival, which tracked rates of major thrombosis, hemorrhage, transformation, and death.

Patients with JAK2V617F mutations were more likely to have a molecular response to ruxolitinib as well as improved outcomes, including progression-free survival (P = .001), event-free survival (P =.001), and overall survival (P =.01).

Mutations in ASXL1 were, however, linked with worse event-free survival (HR, 3.02; P =.003). Additionally, infection rates were more common among patients treated with ruxolitinib.

“These data confirm and challenge the current therapeutic algorithm, supporting the benefit of targeted therapy and molecular monitoring in PV,” the authors wrote in their report.

Disclosures: This research was supported by Novartis. Please see the original reference for a full list of disclosures.


Harrison CN, Nangalia J, Boucher R, et al. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. J Clin Oncol. Published online May 1, 2023. doi:10.1200/JCO.22.01935

This article originally appeared on Hematology Advisor