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Updated: Mar 28, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom
Claire N Harrison1, Jean-Jacques Kiladjian2, J E Hamer-Maansson3
1Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, SE19RT, UK.
Background:
In RESPONSE/RESPONSE-2, ruxolitinib was superior to best available therapy (BAT) in patients with polycythemia vera (PV).
Objective:
Report a post hoc pooled RESPONSE/RESPONSE-2 analysis.
Design:
RESPONSE/RESPONSE-2 were randomized, open-label phase III trials. Adults with hydroxyurea-resistant/intolerant PV were randomized 1:1 to ruxolitinib or BAT; crossover to ruxolitinib was allowed after primary analysis.
Methods:
JAK2V617F allele burden, hematocrit control, and Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) were assessed.
Results:
Among 371 patients, mean JAK2V617F allele burden declined from baseline (ruxolitinib, 66.1%; crossover, 69.5%) through week 208 (41.4%; 37.1%). Significantly more ruxolitinib versus BAT patients achieved hematocrit control at week 28 (62.0% vs 18.2%; p < 0.0001) and ⩾50% reduction in MPN-SAF TSS at week 16 (48.7% vs 18.0%; p < 0.0001).
Conclusion:
Patients receiving ruxolitinib experienced decreased JAK2V617F allele burden, durable hematocrit control, and better symptom improvements versus BAT, reinforcing ruxolitinib clinical benefit.
Trial Registration:
RESPONSE: https://clinicaltrials.gov/study/NCT01243944; RESPONSE-2: https://clinicaltrials.gov/study/NCT02038036.
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