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 - 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 -