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

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...

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Autores principales: Harrison, Claire N., Nangalia, Jyoti, Boucher, Rebecca, Jackson, Aimee, Yap, Christina, O'Sullivan, Jennifer, Fox, Sonia, Ailts, Isaak, Dueck, Amylou C., Geyer, Holly L., Mesa, Ruben A., Dunn, William G., Nadezhdin, Eugene, Curto-Garcia, Natalia, Green, Anna, Wilkins, Bridget, Coppell, Jason, Laurie, John, Garg, Mamta, Ewing, Joanne, Knapper, Steven, Crowe, Josephine, Chen, Frederick, Koutsavlis, Ioannis, Godfrey, Anna, Arami, Siamak, Drummond, Mark, Byrne, Jennifer, Clark, Fiona, Mead-Harvey, Carolyn, Baxter, Elizabeth Joanna, McMullin, Mary Frances, Mead, Adam J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306428/
https://www.ncbi.nlm.nih.gov/pubmed/37126762
http://dx.doi.org/10.1200/JCO.22.01935
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author Harrison, Claire N.
Nangalia, Jyoti
Boucher, Rebecca
Jackson, Aimee
Yap, Christina
O'Sullivan, Jennifer
Fox, Sonia
Ailts, Isaak
Dueck, Amylou C.
Geyer, Holly L.
Mesa, Ruben A.
Dunn, William G.
Nadezhdin, Eugene
Curto-Garcia, Natalia
Green, Anna
Wilkins, Bridget
Coppell, Jason
Laurie, John
Garg, Mamta
Ewing, Joanne
Knapper, Steven
Crowe, Josephine
Chen, Frederick
Koutsavlis, Ioannis
Godfrey, Anna
Arami, Siamak
Drummond, Mark
Byrne, Jennifer
Clark, Fiona
Mead-Harvey, Carolyn
Baxter, Elizabeth Joanna
McMullin, Mary Frances
Mead, Adam J.
author_facet Harrison, Claire N.
Nangalia, Jyoti
Boucher, Rebecca
Jackson, Aimee
Yap, Christina
O'Sullivan, Jennifer
Fox, Sonia
Ailts, Isaak
Dueck, Amylou C.
Geyer, Holly L.
Mesa, Ruben A.
Dunn, William G.
Nadezhdin, Eugene
Curto-Garcia, Natalia
Green, Anna
Wilkins, Bridget
Coppell, Jason
Laurie, John
Garg, Mamta
Ewing, Joanne
Knapper, Steven
Crowe, Josephine
Chen, Frederick
Koutsavlis, Ioannis
Godfrey, Anna
Arami, Siamak
Drummond, Mark
Byrne, Jennifer
Clark, Fiona
Mead-Harvey, Carolyn
Baxter, Elizabeth Joanna
McMullin, Mary Frances
Mead, Adam J.
author_sort Harrison, Claire N.
collection PubMed
description 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.
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spelling pubmed-103064282023-06-29 Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial Harrison, Claire N. Nangalia, Jyoti Boucher, Rebecca Jackson, Aimee Yap, Christina O'Sullivan, Jennifer Fox, Sonia Ailts, Isaak Dueck, Amylou C. Geyer, Holly L. Mesa, Ruben A. Dunn, William G. Nadezhdin, Eugene Curto-Garcia, Natalia Green, Anna Wilkins, Bridget Coppell, Jason Laurie, John Garg, Mamta Ewing, Joanne Knapper, Steven Crowe, Josephine Chen, Frederick Koutsavlis, Ioannis Godfrey, Anna Arami, Siamak Drummond, Mark Byrne, Jennifer Clark, Fiona Mead-Harvey, Carolyn Baxter, Elizabeth Joanna McMullin, Mary Frances Mead, Adam J. J Clin Oncol ORIGINAL REPORTS 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. Wolters Kluwer Health 2023-07-01 2023-05-01 /pmc/articles/PMC10306428/ /pubmed/37126762 http://dx.doi.org/10.1200/JCO.22.01935 Text en © 2023 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle ORIGINAL REPORTS
Harrison, Claire N.
Nangalia, Jyoti
Boucher, Rebecca
Jackson, Aimee
Yap, Christina
O'Sullivan, Jennifer
Fox, Sonia
Ailts, Isaak
Dueck, Amylou C.
Geyer, Holly L.
Mesa, Ruben A.
Dunn, William G.
Nadezhdin, Eugene
Curto-Garcia, Natalia
Green, Anna
Wilkins, Bridget
Coppell, Jason
Laurie, John
Garg, Mamta
Ewing, Joanne
Knapper, Steven
Crowe, Josephine
Chen, Frederick
Koutsavlis, Ioannis
Godfrey, Anna
Arami, Siamak
Drummond, Mark
Byrne, Jennifer
Clark, Fiona
Mead-Harvey, Carolyn
Baxter, Elizabeth Joanna
McMullin, Mary Frances
Mead, Adam J.
Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
title Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
title_full Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
title_fullStr Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
title_full_unstemmed Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
title_short Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
title_sort ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial
topic ORIGINAL REPORTS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306428/
https://www.ncbi.nlm.nih.gov/pubmed/37126762
http://dx.doi.org/10.1200/JCO.22.01935
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