Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial

Srdan Verstovsek, Alessandro M. Vannucchi, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N. Harrison, Fabrizio Pane, Pierre Zachee, Keita Kirito, Carlos Besses, Masayuki Hino, Beatriz Moiraghi, Carole B. Miller, Mario Cazzola, Vittorio Rosti, Igor Blau, Ruben Mesa, Mark M. Jones, Huiling ZhenJingjin Li, Nathalie Francillard, Dany Habr, Jean Jacques Kiladjian

Research output: Article

65 Citations (Scopus)

Abstract

RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7%vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hemat-ocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea- resistant or intolerant patients with polycythemia vera.

Original languageEnglish
Pages (from-to)821-829
Number of pages9
JournalHaematologica
Volume101
Issue number7
DOIs
Publication statusPublished - 2016

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Polycythemia Vera
Spleen
Therapeutics
Hydroxyurea
Hematocrit
Janus Kinase 1
INCB018424
Janus Kinase 2
Safety
Phlebotomy
Hemoglobins
Blood Platelets
Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Verstovsek, S., Vannucchi, A. M., Griesshammer, M., Masszi, T., Durrant, S., Passamonti, F., ... Kiladjian, J. J. (2016). Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica, 101(7), 821-829. https://doi.org/10.3324/haematol.2016.143644

Ruxolitinib versus best available therapy in patients with polycythemia vera : 80-week follow-up from the RESPONSE trial. / Verstovsek, Srdan; Vannucchi, Alessandro M.; Griesshammer, Martin; Masszi, Tamas; Durrant, Simon; Passamonti, Francesco; Harrison, Claire N.; Pane, Fabrizio; Zachee, Pierre; Kirito, Keita; Besses, Carlos; Hino, Masayuki; Moiraghi, Beatriz; Miller, Carole B.; Cazzola, Mario; Rosti, Vittorio; Blau, Igor; Mesa, Ruben; Jones, Mark M.; Zhen, Huiling; Li, Jingjin; Francillard, Nathalie; Habr, Dany; Kiladjian, Jean Jacques.

In: Haematologica, Vol. 101, No. 7, 2016, p. 821-829.

Research output: Article

Verstovsek, S, Vannucchi, AM, Griesshammer, M, Masszi, T, Durrant, S, Passamonti, F, Harrison, CN, Pane, F, Zachee, P, Kirito, K, Besses, C, Hino, M, Moiraghi, B, Miller, CB, Cazzola, M, Rosti, V, Blau, I, Mesa, R, Jones, MM, Zhen, H, Li, J, Francillard, N, Habr, D & Kiladjian, JJ 2016, 'Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial', Haematologica, vol. 101, no. 7, pp. 821-829. https://doi.org/10.3324/haematol.2016.143644
Verstovsek, Srdan ; Vannucchi, Alessandro M. ; Griesshammer, Martin ; Masszi, Tamas ; Durrant, Simon ; Passamonti, Francesco ; Harrison, Claire N. ; Pane, Fabrizio ; Zachee, Pierre ; Kirito, Keita ; Besses, Carlos ; Hino, Masayuki ; Moiraghi, Beatriz ; Miller, Carole B. ; Cazzola, Mario ; Rosti, Vittorio ; Blau, Igor ; Mesa, Ruben ; Jones, Mark M. ; Zhen, Huiling ; Li, Jingjin ; Francillard, Nathalie ; Habr, Dany ; Kiladjian, Jean Jacques. / Ruxolitinib versus best available therapy in patients with polycythemia vera : 80-week follow-up from the RESPONSE trial. In: Haematologica. 2016 ; Vol. 101, No. 7. pp. 821-829.
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T2 - 80-week follow-up from the RESPONSE trial

AU - Verstovsek, Srdan

AU - Vannucchi, Alessandro M.

AU - Griesshammer, Martin

AU - Masszi, Tamas

AU - Durrant, Simon

AU - Passamonti, Francesco

AU - Harrison, Claire N.

AU - Pane, Fabrizio

AU - Zachee, Pierre

AU - Kirito, Keita

AU - Besses, Carlos

AU - Hino, Masayuki

AU - Moiraghi, Beatriz

AU - Miller, Carole B.

AU - Cazzola, Mario

AU - Rosti, Vittorio

AU - Blau, Igor

AU - Mesa, Ruben

AU - Jones, Mark M.

AU - Zhen, Huiling

AU - Li, Jingjin

AU - Francillard, Nathalie

AU - Habr, Dany

AU - Kiladjian, Jean Jacques

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N2 - RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7%vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hemat-ocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea- resistant or intolerant patients with polycythemia vera.

AB - RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7%vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hemat-ocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea- resistant or intolerant patients with polycythemia vera.

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