Ruxolitinib versus standard therapy for the treatment of polycythemia vera

Alessandro M. Vannucchi, Jean Jacques Kiladjian, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N. Harrison, Fabrizio Pane, Pierre Zachee, Ruben Mesa, Shui He, Mark M. Jones, William Garrett, Jingjin Li, Ulrich Pirron, Dany Habr, Srdan Verstovsek

Research output: Contribution to journalArticle

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Abstract

Background Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea.

Methods We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1: 1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging.

Results The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P = 0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard- therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy.

Conclusions In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.

Original languageEnglish (US)
Pages (from-to)426-435
Number of pages10
JournalNew England Journal of Medicine
Volume372
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Polycythemia Vera
Group Psychotherapy
Therapeutics
Hematocrit
Hydroxyurea
Spleen
INCB018424
Janus Kinase 1
Janus Kinase 2
Phlebotomy
Splenomegaly
Herpes Zoster

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vannucchi, A. M., Kiladjian, J. J., Griesshammer, M., Masszi, T., Durrant, S., Passamonti, F., ... Verstovsek, S. (2015). Ruxolitinib versus standard therapy for the treatment of polycythemia vera. New England Journal of Medicine, 372(5), 426-435. https://doi.org/10.1056/NEJMoa1409002

Ruxolitinib versus standard therapy for the treatment of polycythemia vera. / Vannucchi, Alessandro M.; Kiladjian, Jean Jacques; Griesshammer, Martin; Masszi, Tamas; Durrant, Simon; Passamonti, Francesco; Harrison, Claire N.; Pane, Fabrizio; Zachee, Pierre; Mesa, Ruben; He, Shui; Jones, Mark M.; Garrett, William; Li, Jingjin; Pirron, Ulrich; Habr, Dany; Verstovsek, Srdan.

In: New England Journal of Medicine, Vol. 372, No. 5, 01.01.2015, p. 426-435.

Research output: Contribution to journalArticle

Vannucchi, AM, Kiladjian, JJ, Griesshammer, M, Masszi, T, Durrant, S, Passamonti, F, Harrison, CN, Pane, F, Zachee, P, Mesa, R, He, S, Jones, MM, Garrett, W, Li, J, Pirron, U, Habr, D & Verstovsek, S 2015, 'Ruxolitinib versus standard therapy for the treatment of polycythemia vera', New England Journal of Medicine, vol. 372, no. 5, pp. 426-435. https://doi.org/10.1056/NEJMoa1409002
Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. New England Journal of Medicine. 2015 Jan 1;372(5):426-435. https://doi.org/10.1056/NEJMoa1409002
Vannucchi, Alessandro M. ; Kiladjian, Jean Jacques ; Griesshammer, Martin ; Masszi, Tamas ; Durrant, Simon ; Passamonti, Francesco ; Harrison, Claire N. ; Pane, Fabrizio ; Zachee, Pierre ; Mesa, Ruben ; He, Shui ; Jones, Mark M. ; Garrett, William ; Li, Jingjin ; Pirron, Ulrich ; Habr, Dany ; Verstovsek, Srdan. / Ruxolitinib versus standard therapy for the treatment of polycythemia vera. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 5. pp. 426-435.
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T1 - Ruxolitinib versus standard therapy for the treatment of polycythemia vera

AU - Vannucchi, Alessandro M.

AU - Kiladjian, Jean Jacques

AU - Griesshammer, Martin

AU - Masszi, Tamas

AU - Durrant, Simon

AU - Passamonti, Francesco

AU - Harrison, Claire N.

AU - Pane, Fabrizio

AU - Zachee, Pierre

AU - Mesa, Ruben

AU - He, Shui

AU - Jones, Mark M.

AU - Garrett, William

AU - Li, Jingjin

AU - Pirron, Ulrich

AU - Habr, Dany

AU - Verstovsek, Srdan

PY - 2015/1/1

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N2 - Background Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea.Methods We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1: 1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging.Results The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P = 0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard- therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy.Conclusions In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.

AB - Background Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea.Methods We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1: 1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging.Results The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P = 0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard- therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy.Conclusions In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.

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