Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide.
Date
2017-10ICR Author
Author
Harrison, CN
Mead, AJ
Panchal, A
Fox, S
Yap, C
Gbandi, E
Houlton, A
Alimam, S
Ewing, J
Wood, M
Chen, F
Coppell, J
Panoskaltsis, N
Knapper, S
Ali, S
Hamblin, A
Scherber, R
Dueck, AC
Cross, NCP
Mesa, R
McMullin, MF
Type
Journal Article
Metadata
Show full item recordAbstract
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 2 trial of ruxolitinib (JAK1/2 inhibitor) vs best available therapy (BAT) in ET and polycythemia vera patients resistant or intolerant to HC. Here, findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 and 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 2 complete molecular responses (CMR) and 1 partial molecular response in CALR- positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in 1 CMR patient, presumably because of the emergence of a different clone, raising questions about the relevance of CMR in ET patients. Grade 3 and 4 anemia occurred in 19% and 0% of ruxolitinib vs 0% (both grades) in the BAT arm, and grade 3 and 4 thrombocytopenia in 5.2% and 1.7% of ruxolitinib vs 0% (both grades) of BAT-treated patients. Rates of discontinuation or treatment switching did not differ between the 2 trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET. This trial was registered at www.isrctn.com as #ISRCTN61925716.
Collections
Subject
Humans
Disease Progression
Hemorrhage
Hydroxyurea
Pyrazoles
Treatment Outcome
Withholding Treatment
Drug Resistance
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Thrombocythemia, Essential
Research team
Clinical Trials & Statistics Unit
Language
eng
Date accepted
2017-07-24
License start date
2017-10
Citation
Blood, 2017, 130 (17), pp. 1889 - 1897