Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial
<p>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 (ISRCTN619257...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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American Society of Hematology
2017
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| _version_ | 1797100181745827840 |
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| author | Harrison, C Mead, A 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, A Cross, N Mesa, R McMullin, M |
| author_facet | Harrison, C Mead, A 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, A Cross, N Mesa, R McMullin, M |
| author_sort | Harrison, C |
| collection | OXFORD |
| description | <p>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.</p> |
| first_indexed | 2024-03-07T05:34:06Z |
| format | Journal article |
| id | oxford-uuid:e34431b4-d012-413f-80b7-afd083002a97 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:34:06Z |
| publishDate | 2017 |
| publisher | American Society of Hematology |
| record_format | dspace |
| spelling | oxford-uuid:e34431b4-d012-413f-80b7-afd083002a972022-03-27T10:08:12ZRuxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e34431b4-d012-413f-80b7-afd083002a97Symplectic Elements at OxfordAmerican Society of Hematology2017Harrison, CMead, APanchal, AFox, SYap, CGbandi, EHoulton, AAlimam, SEwing, JWood, MChen, FCoppell, JPanoskaltsis, NKnapper, SAli, SHamblin, AScherber, RDueck, ACross, NMesa, RMcMullin, M<p>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.</p> |
| spellingShingle | Harrison, C Mead, A 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, A Cross, N Mesa, R McMullin, M Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial |
| title | Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial |
| title_full | Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial |
| title_fullStr | Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial |
| title_full_unstemmed | Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial |
| title_short | Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial |
| title_sort | ruxolitinib versus best available therapy for et intolerant or resistant to hydroxycarbamide in a randomized trial |
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