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.
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.
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 ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.