Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a...

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by JAK/STAT pathway activation.
• High-risk PV patients often experience thrombotic events, systemic symptoms, and disease transformation.
• Ruxolitinib is an effective treatment for controlling blood counts and alleviating symptoms in high-risk PV.

Purpose of the Study:

• To evaluate the efficacy of ruxolitinib compared to best available therapy (BAT) in patients with hydroxycarbamide-resistant or intolerant polycythemia vera (HC-INT/RES).
• To assess outcomes including complete response (CR), duration of response, event-free survival (EFS), symptom control, and molecular response.

Main Methods:

• The MAJIC-PV trial was a randomized phase II study.
• 180 patients with HC-INT/RES PV were randomized to receive either ruxolitinib or BAT.
• Primary endpoint was CR within 1 year; secondary endpoints included duration of response, EFS, symptom burden, and molecular response.

Main Results:

• Ruxolitinib achieved a significantly higher CR rate (43%) compared to BAT (26%) (P = .02).
• Ruxolitinib demonstrated superior duration of CR, symptom response, and event-free survival (EFS).
• Molecular response, indicated by a reduced JAK2V617F variant allele fraction, was more frequent with ruxolitinib and correlated with improved progression-free survival (PFS), EFS, and overall survival (OS).

Conclusions:

• Ruxolitinib offers significant benefits for HC-INT/RES PV patients, improving CR, EFS, and molecular response.
• This study provides the first evidence linking molecular response to improved EFS, PFS, and OS in PV patients treated with ruxolitinib.
• Ruxolitinib is a valuable therapeutic option for patients with polycythemia vera resistant or intolerant to hydroxycarbamide.