Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 41(2023), 19 vom: 01. Juli, Seite 3534-3544 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Harrison, Claire N [VerfasserIn] |
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| Links: |
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| Themen: |
82S8X8XX8H |
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| Anmerkungen: |
Date Completed 30.06.2023 Date Revised 13.03.2024 published: Print-Electronic ISRCTN: ISRCTN61925716 Citation Status MEDLINE |
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| doi: |
10.1200/JCO.22.01935 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356301192 |
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| 245 | 1 | 0 | |a Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 30.06.2023 | ||
| 500 | |a Date Revised 13.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ISRCTN: ISRCTN61925716 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a ruxolitinib |2 NLM | |
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| 700 | 1 | |a Dueck, Amylou C |e verfasserin |4 aut | |
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| 700 | 1 | |a Mesa, Ruben A |e verfasserin |4 aut | |
| 700 | 1 | |a Dunn, William G |e verfasserin |4 aut | |
| 700 | 1 | |a Nadezhdin, Eugene |e verfasserin |4 aut | |
| 700 | 1 | |a Curto-Garcia, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Wilkins, Bridget |e verfasserin |4 aut | |
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| 700 | 1 | |a Laurie, John |e verfasserin |4 aut | |
| 700 | 1 | |a Garg, Mamta |e verfasserin |4 aut | |
| 700 | 1 | |a Ewing, Joanne |e verfasserin |4 aut | |
| 700 | 1 | |a Knapper, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Crowe, Josephine |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Frederick |e verfasserin |4 aut | |
| 700 | 1 | |a Koutsavlis, Ioannis |e verfasserin |4 aut | |
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