Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea: European observational study.
hematocrit
phlebotomy
polycythemia vera
ruxolitinib
splenomegaly
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
30 Oct 2023
30 Oct 2023
Historique:
revised:
11
10
2023
received:
26
05
2023
accepted:
12
10
2023
medline:
30
10
2023
pubmed:
30
10
2023
entrez:
30
10
2023
Statut:
aheadofprint
Résumé
Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%-24% of PV patients report intolerance and resistance to HU. This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients. In the 350 enrolled patients, 70% were >60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit <45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related. This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.
Sections du résumé
BACKGROUND
BACKGROUND
Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%-24% of PV patients report intolerance and resistance to HU.
METHODS
METHODS
This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients.
RESULTS
RESULTS
In the 350 enrolled patients, 70% were >60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit <45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related.
CONCLUSION
CONCLUSIONS
This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Novartis Pharma
Informations de copyright
© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
Références
Spivak JL. Myeloproliferative neoplasms. New Engl J Med. 2017;376(22):2168-2181.
Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874-1881.
Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23(10):2224-2232.
Griesshammer M, Gisslinger H, Mesa R. Current and future treatment options for polycythemia vera. Ann Hematol. 2015;94(6):901-910.
Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR. Therapeutic recommendations in polycythemia vera based on polycythemia vera study group protocols. Semin Hematol. 1986;23(2):132-143.
Stuart BJ, Viera AJ. Polycythemia vera. Am Fam Physician. 2004;69(9):2139-2144.
Mesa RA, Niblack J, Wadleigh M, et al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international internet-based survey of 1179 MPD patients. Cancer. 2007;109(1):68-76.
Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013;121(23):4778-4781.
Kiladjian JJ, Winton EF, Talpaz M, Verstovsek S. Ruxolitinib for the treatment of patients with polycythemia vera. Expert Rev Hematol. 2015;8(4):391-401.
Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33.
Panova-Noeva M, Marchetti M, Russo L, et al. ADP-induced platelet aggregation and thrombin generation are increased in essential thrombocythemia and polycythemia vera. Thromb Res. 2013;132(1):88-93.
Patrono C, Rocca B, De Stefano V. Platelet activation and inhibition in polycythemia vera and essential thrombocythemia. Blood. 2013;121(10):1701-1711.
Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761-770.
Barbui T, Finazzi G, Carobbio A, et al. Development and validation of an international prognostic score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128-5133. quiz 5252.
Geyer H, Scherber R, Kosiorek H, et al. Symptomatic profiles of patients with polycythemia vera: implications of inadequately controlled disease. J Clin Oncol. 2016;34(2):151-159.
Emanuel RM, Dueck AC, Geyer HL, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol. 2012;30(33):4098-4103.
Randi ML, Ruzzon E, Luzzatto G, Tezza F, Girolami A, Fabris F. Safety profile of hydroxyurea in the treatment of patients with Philadelphia-negative chronic myeloproliferative disorders. Haematologica. 2005;90(2):261-262.
Alvarez-Larrán A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood. 2012;119(6):1363-1369.
Alvarez-Larrán A, Kerguelen A, Hernández-Boluda JC, et al. Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br J Haematol. 2016;172(5):786-793.
Marchetti M, Vannucchi AM, Griesshammer M, et al. Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations. Lancet Haematol. 2022;9(4):e301-e311.
Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426-435.
Passamonti F, Griesshammer M, Palandri F, et al. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017;18(1):88-99.
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics. 1993;4(5):353-365.
Moulard O, Mehta J, Fryzek J, Olivares R, Iqbal U, Mesa RA. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. Eur J Haematol. 2014;92(4):289-297.
Verstovsek S, Vannucchi AM, Griesshammer M, et al. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica. 2016;101(7):821-829.
Harrison CN, Koschmieder S, Foltz L, et al. The impact of myeloproliferative neoplasms (MPNs) on patient quality of life and productivity: results from the international MPN landmark survey. Ann Hematol. 2017;96(10):1653-1665.
Harrison CN, Nangalia J, Boucher R, et al. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. J Clin Oncol. 2023;41(19):3534-3544.
Cattaneo D, Iurlo A. Immune dysregulation and infectious complications in MPN patients treated with JAK inhibitors. Front Immunol. 2021;12:750346.
Finazzi G, Caruso V, Marchioli R, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105(7):2664-2670.