Ruxolitinib vs best available therapy for et intolerant or resistant to hydroxycarbamide

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, Robyn Scherber, Amylou C. Dueck, Nicholas C.P. Cross, Ruben Mesa & 1 others Mary Frances McMullin

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1889-1897
Number of pages9
JournalBlood
Volume130
Issue number17
DOIs
StatePublished - Oct 26 2017
Externally publishedYes

Fingerprint

Essential Thrombocythemia
Primary Myelofibrosis
Therapeutics
Thrombosis
Hemorrhage
INCB018424
Thrombocytosis
Polycythemia Vera
Anemia
Leukemia
Clone Cells
Population

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Harrison, C. N., Mead, A. J., Panchal, A., Fox, S., Yap, C., Gbandi, E., ... McMullin, M. F. (2017). Ruxolitinib vs best available therapy for et intolerant or resistant to hydroxycarbamide. Blood, 130(17), 1889-1897. https://doi.org/10.1182/blood-2017-05-785790

Ruxolitinib vs best available therapy for et intolerant or resistant to hydroxycarbamide. / Harrison, Claire N.; Mead, Adam J.; Panchal, Anesh; Fox, Sonia; Yap, Christina; Gbandi, Emmanouela; Houlton, Aimee; Alimam, Samah; Ewing, Joanne; Wood, Marion; Chen, Frederick; Coppell, Jason; Panoskaltsis, Nicki; Knapper, Steven; Ali, Sahra; Hamblin, Angela; Scherber, Robyn; Dueck, Amylou C.; Cross, Nicholas C.P.; Mesa, Ruben; McMullin, Mary Frances.

In: Blood, Vol. 130, No. 17, 26.10.2017, p. 1889-1897.

Research output: Contribution to journalArticle

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 vs best available therapy for et intolerant or resistant to hydroxycarbamide', Blood, vol. 130, no. 17, pp. 1889-1897. https://doi.org/10.1182/blood-2017-05-785790
Harrison CN, Mead AJ, Panchal A, Fox S, Yap C, Gbandi E et al. Ruxolitinib vs best available therapy for et intolerant or resistant to hydroxycarbamide. Blood. 2017 Oct 26;130(17):1889-1897. https://doi.org/10.1182/blood-2017-05-785790
Harrison, Claire N. ; Mead, Adam J. ; Panchal, Anesh ; Fox, Sonia ; Yap, Christina ; Gbandi, Emmanouela ; Houlton, Aimee ; Alimam, Samah ; Ewing, Joanne ; Wood, Marion ; Chen, Frederick ; Coppell, Jason ; Panoskaltsis, Nicki ; Knapper, Steven ; Ali, Sahra ; Hamblin, Angela ; Scherber, Robyn ; Dueck, Amylou C. ; Cross, Nicholas C.P. ; Mesa, Ruben ; McMullin, Mary Frances. / Ruxolitinib vs best available therapy for et intolerant or resistant to hydroxycarbamide. In: Blood. 2017 ; Vol. 130, No. 17. pp. 1889-1897.
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abstract = "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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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

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