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

Claire N Harrison; Adam J Mead; Anesh Panchal; Sonia Fox; Christina Yap; Emmanouela Gbandi; Aimee Houlton; Samah Alimam; Joanne Ewing; Marion Wood; Frederick Chen; Jason Coppell; Nicki Panoskaltsis; Steven Knapper; Sahra Ali; Angela Hamblin; Ruben Scherber; Amylou C Dueck; Nicholas C P Cross; Ruben Mesa; Mary Frances McMullin

doi:10.1182/blood-2017-05-785790

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

Claire N Harrison, Adam J Mead, Anesh Panchal, Sonia Fox, Christina Yap, Emmanouela Gbandi, Aimee Houlton, Samah Alimam, Joanne Ewing, Marion Wood, Frederick Chen, Jason Coppell, Nicki Panoskaltsis, Steven Knapper, Sahra Ali, Angela Hamblin, Ruben Scherber, Amylou C Dueck, Nicholas C P Cross, Ruben MesaMary Frances McMullin

Cancer Clinical Trials Unit

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66 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1889-1897
Journal	Blood
Volume	130
Issue number	17
DOIs	https://doi.org/10.1182/blood-2017-05-785790
Publication status	Published - 26 Oct 2017

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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, J., Panoskaltsis, N., Knapper, S., Ali, S., Hamblin, A., Scherber, R., Dueck, A. C., Cross, N. C. P., ... McMullin, M. F. (2017). Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial. Blood, 130(17), 1889-1897. https://doi.org/10.1182/blood-2017-05-785790

@article{f2c4a95faef84beda493b24530cbe116,

title = "Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial",

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.",

author = "Harrison, {Claire N} and Mead, {Adam J} and Anesh Panchal and Sonia Fox and Christina Yap and Emmanouela Gbandi and Aimee Houlton and Samah Alimam and Joanne Ewing and Marion Wood and Frederick Chen and Jason Coppell and Nicki Panoskaltsis and Steven Knapper and Sahra Ali and Angela Hamblin and Ruben Scherber and Dueck, {Amylou C} and Cross, {Nicholas C P} and Ruben Mesa and McMullin, {Mary Frances}",

note = "Copyright {\textcopyright} 2017 American Society of Hematology.",

year = "2017",

month = oct,

day = "26",

doi = "10.1182/blood-2017-05-785790",

language = "English",

volume = "130",

pages = "1889--1897",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

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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 2017, 'Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial', Blood, vol. 130, no. 17, pp. 1889-1897. https://doi.org/10.1182/blood-2017-05-785790

TY - JOUR

T1 - Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial

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, Ruben

AU - Dueck, Amylou C

AU - Cross, Nicholas C P

AU - Mesa, Ruben

AU - McMullin, Mary Frances

PY - 2017/10/26

Y1 - 2017/10/26

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2017-05-785790

DO - 10.1182/blood-2017-05-785790

M3 - Article

C2 - 28794072

SN - 0006-4971

VL - 130

SP - 1889

EP - 1897

JO - Blood

JF - Blood

IS - 17

ER -

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

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