Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620462
Title:
Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial.
Authors:
Harrison, C. N.; Mead, A. J.; Panchal, A.; Fox, S.; Yap, C.; Gbandi, E.; Houlton, A.; Alimam, S.; Ewing, J.; Wood, M.; Chen, F.; Coppell, Jason; Panoskaltsis, N.; Knapper, S.; Ali, S.; Hamblin, A.; Scherber, R.; Dueck, A. C.; Cross, N. C. P.; Mesa, R.; McMullin, M. F.
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.
Citation:
Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial. 2017 Oct 26;130(17):1889-1897 Blood
Publisher:
American Society of Hematology
Journal:
Blood
Issue Date:
9-Aug-2017
URI:
http://hdl.handle.net/11287/620462
DOI:
10.1182/blood-2017-05-785790
PubMed ID:
28794072
Additional Links:
https://doi.org/10.1182/blood-2017-05-785790
Type:
Journal Article
Language:
en
ISSN:
1528-0020
Appears in Collections:
Clinical Haematology; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHarrison, C. N.en
dc.contributor.authorMead, A. J.en
dc.contributor.authorPanchal, A.en
dc.contributor.authorFox, S.en
dc.contributor.authorYap, C.en
dc.contributor.authorGbandi, E.en
dc.contributor.authorHoulton, A.en
dc.contributor.authorAlimam, S.en
dc.contributor.authorEwing, J.en
dc.contributor.authorWood, M.en
dc.contributor.authorChen, F.en
dc.contributor.authorCoppell, Jasonen
dc.contributor.authorPanoskaltsis, N.en
dc.contributor.authorKnapper, S.en
dc.contributor.authorAli, S.en
dc.contributor.authorHamblin, A.en
dc.contributor.authorScherber, R.en
dc.contributor.authorDueck, A. C.en
dc.contributor.authorCross, N. C. P.en
dc.contributor.authorMesa, R.en
dc.contributor.authorMcMullin, M. F.en
dc.date.accessioned2017-10-19T10:46:26Z-
dc.date.available2017-10-19T10:46:26Z-
dc.date.issued2017-08-09-
dc.identifier.citationRuxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial. 2017 Oct 26;130(17):1889-1897 Blooden
dc.identifier.issn1528-0020-
dc.identifier.pmid28794072-
dc.identifier.doi10.1182/blood-2017-05-785790-
dc.identifier.urihttp://hdl.handle.net/11287/620462-
dc.description.abstractTreatments 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.en
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.relation.urlhttps://doi.org/10.1182/blood-2017-05-785790en
dc.rightsArchived with thanks to Blooden
dc.subjectWessex Classification Subject Headings::Haematologyen
dc.titleRuxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial.en
dc.typeJournal Articleen
dc.identifier.journalBlooden
dc.type.versionPublisheden

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