Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial
Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P=.40). At 2 years rates of thrombosis, hemorrhage and transformation were not significantly different, however some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were two complete molecular responses (CMR) and one partial molecular response (PMR) in CALR positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in one CMR patient, presumably due to the emergence of a different clone raising questions about the relevance of CMR in ET patients. Grade 3&4 anemia occurred in 19% & 0% of ruxolitinib vs 0% (both grades) BAT arm, grade 3&4 thrombocytopenia in 5.2% & 1.7% of ruxolitinib vs 0% (both grades) of BAT treated patients. Rates of discontinuation or treatment switching did not differ between the two trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET.
Journal Article
1889-1897
Harrison, Claire N.
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Mead, Adam J.
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Panchal, Anesh
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Fox, Sonia
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Yap, Christina
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Gbandi, Emmanouela
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Houlton, Aimee
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Alimam, Samah
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Ewing, Joanne
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Wood, Marion
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Chen, Frederick
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Coppell, Jason
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Panoskaltsis, Nicki
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Knapper, Steven
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Ali, Sahra
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Hamblin, Angela
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Scherber, Ruben
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Dueck, Amylou C.
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Cross, Nicholas C.P.
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Mesa, Ruben
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McMullin, Mary Frances
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26 October 2017
Harrison, Claire N.
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Mead, Adam J.
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Panchal, Anesh
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Fox, Sonia
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Yap, Christina
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Gbandi, Emmanouela
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Houlton, Aimee
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Alimam, Samah
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Ewing, Joanne
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Wood, Marion
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Chen, Frederick
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Coppell, Jason
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Panoskaltsis, Nicki
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Knapper, Steven
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Ali, Sahra
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Hamblin, Angela
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Scherber, Ruben
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Dueck, Amylou C.
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Cross, Nicholas C.P.
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Mesa, Ruben
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McMullin, Mary Frances
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Harrison, Claire N., Mead, Adam J., Panchal, Anesh, Fox, Sonia, Yap, Christina, Gbandi, Emmanouela, Houlton, Aimee, Alimam, Samah, Ewing, Joanne, Wood, Marion, Chen, Frederick, Coppell, Jason, Panoskaltsis, Nicki, Knapper, Steven, Ali, Sahra, Hamblin, Angela, Scherber, Ruben, Dueck, Amylou C., Cross, Nicholas C.P., Mesa, Ruben and McMullin, Mary Frances
(2017)
Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial.
Blood, 130 (17), .
(doi:10.1182/blood-2017-05-785790).
Abstract
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P=.40). At 2 years rates of thrombosis, hemorrhage and transformation were not significantly different, however some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were two complete molecular responses (CMR) and one partial molecular response (PMR) in CALR positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in one CMR patient, presumably due to the emergence of a different clone raising questions about the relevance of CMR in ET patients. Grade 3&4 anemia occurred in 19% & 0% of ruxolitinib vs 0% (both grades) BAT arm, grade 3&4 thrombocytopenia in 5.2% & 1.7% of ruxolitinib vs 0% (both grades) of BAT treated patients. Rates of discontinuation or treatment switching did not differ between the two trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET.
Text
blood-2017-05-785790.full
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Accepted/In Press date: 24 July 2017
e-pub ahead of print date: 9 August 2017
Published date: 26 October 2017
Keywords:
Journal Article
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Local EPrints ID: 415358
URI: http://eprints.soton.ac.uk/id/eprint/415358
ISSN: 0006-4971
PURE UUID: b5c72d1f-0b16-4d3f-878d-4ec9e1581649
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Date deposited: 07 Nov 2017 17:31
Last modified: 16 Mar 2024 05:39
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Contributors
Author:
Claire N. Harrison
Author:
Adam J. Mead
Author:
Anesh Panchal
Author:
Sonia Fox
Author:
Christina Yap
Author:
Emmanouela Gbandi
Author:
Aimee Houlton
Author:
Samah Alimam
Author:
Joanne Ewing
Author:
Marion Wood
Author:
Frederick Chen
Author:
Jason Coppell
Author:
Nicki Panoskaltsis
Author:
Steven Knapper
Author:
Sahra Ali
Author:
Angela Hamblin
Author:
Ruben Scherber
Author:
Amylou C. Dueck
Author:
Ruben Mesa
Author:
Mary Frances McMullin
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