Ruxolitinib for Patients With Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide

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In a UK phase II trial (MAJIC-PV) reported in the Journal of Clinical Oncology, Harrison et al found that ruxolitinib produced a higher complete response rate vs best available therapy in patients with polycythemia vera intolerant of or resistant to hydroxycarbamide.

Study Details

In the multicenter open-label trial, 180 patients were randomly assigned between August 2012 and August 2016 to receive ruxolitinib (n = 93) starting at 10 mg twice daily (5 mg twice daily for patients with baseline platelets of  100–200 × 109/L) or best available therapy (n = 87); the most commonly used best available therapies were hydroxycarbamide (32%), interferon (15%), and the combination of the two (12%). The primary outcome measure was complete response within 1 year.

Key Findings

Median follow-up at data cutoff in April 2022 was 4.8 years. Complete response within 1 year was achieved in 40 patients (43%) in the ruxolitinib group vs 23 (26%) in the best available therapy group (odds ratio = 2.12, 90% confidence interval [CI] = 1.25–3.60, P = .02). Duration of complete response was significantly prolonged in the ruxolitinib group (hazard ratio [HR] = 0.38, 95% CI = 0.24–0.61, P < .001).

Among 115 evaluable patients, Myeloproliferative Neoplasm–Symptom Assessment Form total symptom scores were reduced by ≥ 50% in 61% of patients in the ruxolitinib group vs 30% of the best available therapy group at least one time point (P = .001).

The ruxolitinib group had significantly better event-free survival (events = major thrombosis, hemorrhage, transformation, and death) vs the best available therapy group (HR = 0.58, 95% CI = 0.35–0.94, P = .03). Achievement of complete response within 1 year was also associated with improved event-free survival (HR = 0.41, 95% CI = 0.21–0.78, P = .01).

Analysis of  JAK2V617F variant allele fraction (VAF) showed that molecular response (JAK2 VAF reduction of > 50%) at the last recorded time point was more common among evaluable patients in the in the ruxolitinib group (39/70 = 56%) vs the best available therapy group (14/57 = 25%) and was associated with improved progression-free survival (P = .001), event-free survival (P = .001), and overall survival (P = .01). Presence of ASXL1 mutations was associated with significantly poorer event-free survival (HR = 3.02, 95% CI = 1.47–6.17, P = .003).

Infections were more common in the ruxolitinib vs best available therapy group, with a total of 27 vs 12 grade 3 or 4 infections observed; no infection-related deaths or atypical infections were observed. Squamous cell skin cancer was more common in the ruxolitinib group (11 vs 0 events).

The investigators concluded, “The MAJIC-PV study demonstrates ruxolitinib treatment benefits patients with polycythemia vera with resistance/intolerance to hydroxycarbamide, with superior complete response and event-free survival as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to event-free, progression-free, and overall survival.”

Claire N. Harrison, DM, FRCP, of Guy’s and St Thomas’ NHS Foundation Trust, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Blood Cancer UK and Novartis. For full disclosures of the study authors, visit

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