TY - JOUR
T1 - Ruxolitinib vs best available therapy for et intolerant or resistant to hydroxycarbamide
AU - Harrison, Claire N.
AU - Mead, Adam J.
AU - Panchal, Anesh
AU - Fox, Sonia
AU - Yap, Christina
AU - Gbandi, Emmanouela
AU - Houlton, Aimee
AU - Alimam, Samah
AU - Ewing, Joanne
AU - Wood, Marion
AU - Chen, Frederick
AU - Coppell, Jason
AU - Panoskaltsis, Nicki
AU - Knapper, Steven
AU - Ali, Sahra
AU - Hamblin, Angela
AU - Scherber, Robyn
AU - Dueck, Amylou C.
AU - Cross, Nicholas C.P.
AU - Mesa, Ruben
AU - McMullin, Mary Frances
N1 - Funding Information:
This trial is funded by Bloodwise under the Trials Acceleration Program. An unrestricted educational grant was provided to support the trial and adjunctive science by Novartis. Ruxolitinib was provided free of charge by Novartis. C.Y. was funded by grant C22436/A15958 from Cancer Research UK.
Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/10/26
Y1 - 2017/10/26
N2 - Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, diseaserelated 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.Therewasnoevidenceof improvement incomplete responsewithin1year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P 5.40). At 2 years, rates of thrombosis, hemorrhage, and transformationwere not significantly different; however, some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT.Molecular responses were uncommon; there were 2 completemolecular 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 treatmentswitching didnot differ between the 2 trial arms. TheMAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET.
AB - Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, diseaserelated 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.Therewasnoevidenceof improvement incomplete responsewithin1year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P 5.40). At 2 years, rates of thrombosis, hemorrhage, and transformationwere not significantly different; however, some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT.Molecular responses were uncommon; there were 2 completemolecular 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 treatmentswitching didnot differ between the 2 trial arms. TheMAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET.
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U2 - 10.1182/blood-2017-05-785790
DO - 10.1182/blood-2017-05-785790
M3 - Article
C2 - 29074595
AN - SCOPUS:85032495339
SN - 0006-4971
VL - 130
SP - 1889
EP - 1897
JO - Blood
JF - Blood
IS - 17
ER -