Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.
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Embargo End Date
ICR Authors
Authors
Harrison, CN
Nangalia, J
Boucher, R
Jackson, A
Yap, C
O'Sullivan, J
Fox, S
Ailts, I
Dueck, AC
Geyer, HL
Mesa, RA
Dunn, WG
Nadezhdin, E
Curto-Garcia, N
Green, A
Wilkins, B
Coppell, J
Laurie, J
Garg, M
Ewing, J
Knapper, S
Crowe, J
Chen, F
Koutsavlis, I
Godfrey, A
Arami, S
Drummond, M
Byrne, J
Clark, F
Mead-Harvey, C
Baxter, EJ
McMullin, MF
Mead, AJ
Nangalia, J
Boucher, R
Jackson, A
Yap, C
O'Sullivan, J
Fox, S
Ailts, I
Dueck, AC
Geyer, HL
Mesa, RA
Dunn, WG
Nadezhdin, E
Curto-Garcia, N
Green, A
Wilkins, B
Coppell, J
Laurie, J
Garg, M
Ewing, J
Knapper, S
Crowe, J
Chen, F
Koutsavlis, I
Godfrey, A
Arami, S
Drummond, M
Byrne, J
Clark, F
Mead-Harvey, C
Baxter, EJ
McMullin, MF
Mead, AJ
Document Type
Journal Article
Date
2023-07-01
Date Accepted
2023-03-21
Abstract
PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.
Citation
Journal of Clinical Oncology, 2023, pp. JCO2201935 -
Source Title
Journal of Clinical Oncology
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
0732-183X
eISSN
1527-7755
1527-7755
1527-7755
Collections
Research Team
Clin Trials & Stats Unit