Ruxolitinib for the treatment of patients with polycythemia vera

References

• Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937-51
   PubMed Web of Science ®Google Scholar
• Barbui T, Finazzi G, Falanga A. Myeloproliferative neoplasms and thrombosis. Blood 2013;122:2176-84
   PubMed Web of Science ®Google Scholar
• Mehta J, Wang H, Iqbal SU, et al. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma 2014;55:595-600
   PubMed Web of Science ®Google Scholar
• Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 2006;32:171-3
   PubMed Web of Science ®Google Scholar
• Passamonti F, Rumi E, Pietra D, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 2010;24:1574-9
   PubMed Web of Science ®Google Scholar
• Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61
   PubMed Web of Science ®Google Scholar
• Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management. Am J Hematol 2015;90:162-73
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian H, Cortes J, et al. Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov 2011;10:127-40
   PubMed Web of Science ®Google Scholar
• James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005;434:1144-8
   PubMed Web of Science ®Google Scholar
• Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-90
   PubMed Web of Science ®Google Scholar
• Bartley TD, Bogenberger J, Hunt P, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 1994;77:1117-24
   PubMed Web of Science ®Google Scholar
• Drachman JG, Millett KM, Kaushansky K. Thrombopoietin signal transduction requires functional JAK2, not TYK2. J Biol Chem 1999;274:13480-4
   PubMed Web of Science ®Google Scholar
• Wang L, Xue J, Zadorozny EV, et al. G-CSF stimulates Jak2-dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation. Cell Signal 2008;20:1890-9
   PubMed Web of Science ®Google Scholar
• Vannucchi AM, Antonioli E, Guglielmelli P, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia 2007;21:1952-9
   PubMed Web of Science ®Google Scholar
• Gattermann N, Billiet J, Kronenwett R, et al. High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count>600x109/L) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable. Blood 2007;109:1334-5
   PubMed Web of Science ®Google Scholar
• 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;30:4098-103
   PubMed Web of Science ®Google Scholar
• Johansson P, Mesa R, Scherber R, et al. Association between quality of life and clinical parameters in patients with myeloproliferative neoplasms. Leuk Lymphoma 2012;53:441-4
   PubMed Web of Science ®Google Scholar
• Scherber R, Dueck AC, Johansson P, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 2011;118:401-8
   PubMed Web of Science ®Google Scholar
• 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;109:68-76
   PubMed Web of Science ®Google Scholar
• Siegel FP, Tauscher J, Petrides PE. Aquagenic pruritus in polycythemia vera: characteristics and influence on quality of life in 441 patients. Am J Hematol 2013;88:665-9
   PubMed Web of Science ®Google Scholar
• Diehn F, Tefferi A. Pruritus in polycythaemia vera: prevalence, laboratory correlates and management. Br J Haematol 2001;115:619-21
   PubMed Web of Science ®Google Scholar
• Finelli C, Gugliotta L, Gamberi B, et al. Relief of intractable pruritus in polycythemia vera with recombinant interferon alfa. Am J Hematol 1993;43:316-18
   PubMed Web of Science ®Google Scholar
• Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013;27:1874-81
   PubMed Web of Science ®Google Scholar
• Gruppo Italiano Studio Policitemia. Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia. Ann Intern Med 1995;123:656-64
   PubMed Web of Science ®Google Scholar
• Kiladjian JJ, Chevret S, Dosquet C, et al. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol 2011;29:3907-13
   PubMed Web of Science ®Google Scholar
• Hultcrantz M, Kristinsson SY, Andersson TM, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol 2012;30:2995-3001
   PubMed Web of Science ®Google Scholar
• Vaidya R, Gangat N, Jimma T, et al. Plasma cytokines in polycythemia vera: phenotypic correlates, prognostic relevance, and comparison with myelofibrosis. Am J Hematol 2012;87:1003-5
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer 2014;120:513-20
   PubMed Web of Science ®Google Scholar
• Barbui T, Carobbio A, Finazzi G, et al. Inflammation and thrombosis in essential thrombocythemia and polycythemia vera: different role of C-reactive protein and pentraxin 3. Haematologica 2011;96:315-18
   PubMed Web of Science ®Google Scholar
• Van Rompaey L, Galien R, van der Aar EM, et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol 2013;191:3568-77
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010;115:3109-17
   PubMed Web of Science ®Google Scholar
• Squires M, Harrison CN, Barosi G, et al. The relationship between cytokine levels and symptoms in patients (pts) with myelofibrosis (MF) from COMFORT-II, a phase 3 study of ruxolitinib (RUX) vs best available therapy (BAT) [abstract]. Blood 2013;122:4070
   Google Scholar
• Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004;350:114-24
   PubMed Web of Science ®Google Scholar
• Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013;368:22-33
   PubMed Web of Science ®Google Scholar
• Passamonti F. How I treat polycythemia vera. Blood 2012;120:275-84
   PubMed Web of Science ®Google Scholar
• Alvarez-Larran 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;119:1363-9
   PubMed Web of Science ®Google Scholar
• Scherber R, Dueck AC, Kiladjian JJ, et al. Conventional therapeutic options have limited impact on MPN symptoms: insights from a prospective analysis of the MPN-SAF. Haematologica 2012; abstract 366
   Web of Science ®Google Scholar
• Shilling AD, Nedza FM, Emm T, et al. Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus tyrosine kinase 1/2 inhibitor, in humans. Drug Metab Dispos 2010;38:2023-31
   PubMed Web of Science ®Google Scholar
• JAKAFI® (ruxolitinib) [ package insert Wilmington, DE: Incyte Corporation. 2014
   Google Scholar
• Landolfi R, Di Gennaro L, Barbui T, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood 2007;109:2446-52
   PubMed Web of Science ®Google Scholar
• 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;23:2224-32
   PubMed Web of Science ®Google Scholar
• Barbui T, Finazzi MC, Finazzi G. Front-line therapy in polycythemia vera and essential thrombocythemia. Blood Rev 2012;26:205-11
   PubMed Web of Science ®Google Scholar
• Barosi G, Birgegard G, Finazzi G, et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol 2010;148:961-3
   PubMed Web of Science ®Google Scholar
• 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;29:761-70
   PubMed Web of Science ®Google Scholar
• Kiladjian JJ, Chomienne C, Fenaux P. Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms. Leukemia 2008;22:1990-8
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian HM, Giles F, et al. Pegylated interferon therapy for patients with Philadelphia chromosome-negative myeloproliferative disorders. Semin Thromb Hemost 2006;32:409-16
   PubMed Web of Science ®Google Scholar
• Berk PD, Goldberg JD, Silverstein MN, et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 1981;304:441-7
   PubMed Web of Science ®Google Scholar
• Haanen C, Mathé G, Hayat M, et al. Treatment of polycythaemia vera by radiophosphorus or busulphan: a randomized trial. "Leukemia and Hematosarcoma" Cooperative Group, European Organization for Research on Treatment of Cancer (E.O.R.T.C.). Br J Cancer 1981;44:75-80
   PubMed Web of Science ®Google Scholar
• Fruchtman SM, Mack K, Kaplan ME, et al. From efficacy to safety: a Polycythemia Vera Study Group report on hydroxyurea in patients with polycythemia vera. Semin Hematol 1997;34:17-23
   PubMed Web of Science ®Google Scholar
• Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood 1997;90:3370-7
   PubMed Web of Science ®Google Scholar
• Vannucchi AM. How I treat polycythemia vera. Blood 2014;124:3212-20
   PubMed Web of Science ®Google Scholar
• Deacon B, Abramowitz J. Fear of needles and vasovagal reactions among phlebotomy patients. J Anxiety Disord 2006;20:946-60
   PubMed Web of Science ®Google Scholar
• Hicken BL, Tucker DC, Barton JC. Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis. Am J Gastroenterol 2003;98:2072-7
   PubMed Web of Science ®Google Scholar
• Barton JC, Bottomley SS. Iron deficiency due to excessive therapeutic phlebotomy in hemochromatosis. Am J Hematol 2000;65:223-6
   PubMed Web of Science ®Google Scholar
• Jacob RA, Sandstead HH, Klevay LM, et al. Utility of serum ferritin as a measure of iron deficiency in normal males undergoing repetitive phlebotomy. Blood 1980;56:786-91
   PubMed Web of Science ®Google Scholar
• Best PJ, Petitt RM. Multiple skin cancers associated with hydroxyurea therapy. Mayo Clin Proc 1998;73:961-3
   PubMed Web of Science ®Google Scholar
• Hydrea (hydroxyurea). Full Prescribing Information, Bristol Meyers Squibb Company, Princeton, NJ. 2011
   Google Scholar
• Garcia-Garcia I, Gonzalez-Delgado CA, Valenzuela-Silva CM, et al. Pharmacokinetic and pharmacodynamic comparison of two “pegylated” interferon alpha-2 formulations in healthy male volunteers: a randomized, crossover, double-blind study. BMC Pharmacol 2010;10:15
   PubMedGoogle Scholar
• Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009;27:5418-24
   PubMed Web of Science ®Google Scholar
• Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008;112:3065-72
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Abdel-Wahab O, Manshouri T, et al. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon alpha-2a. Blood 2013;122:893-901
   PubMed Web of Science ®Google Scholar
• Gowin K, Thapaliya P, Samuelson J, et al. Experience with pegylated interferon alpha-2a in advanced myeloproliferative neoplasms in an international cohort of 118 patients. Haematologica 2012;97:1570-3
   PubMed Web of Science ®Google Scholar
• Gisslinger H, Buxhofer-Ausch V, Thaler J, et al. Efficacy and safety of AOP2014/p1101, a novel, investigational mono-pegylated proline-interferon alpha-2b, in patients with polycythemia vera (PV): Update on 51 patients from the ongoing phase I/II Peginvera study. Presented at: ASH; 7-10 December 2013; New Orleans, LA, USA; abstract 4046
   Google Scholar
• Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Available from: https://clinicaltrials.gov/ct2/show/NCT01259856 [Last accessed 6 May 2015]
   Google Scholar
• Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera (PROUD-PV). Available from: https://clinicaltrials.gov/ct2/show/NCT01949805 [Last accessed 6 May 2015]
   Google Scholar
• Mascarenhas J, Mesa R, Prchal J, et al. Optimal therapy for polycythemia vera and essential thrombocythemia can only be determined by the completion of randomized clinical trials. Haematologica 2014;99:945-9
   PubMed Web of Science ®Google Scholar
• Skov V, Larsen TS, Thomassen M, et al. Increased gene expression of histone deacetylases in patients with Philadelphia-negative chronic myeloproliferative neoplasms. Leuk Lymphoma 2012;53:123-9
   PubMed Web of Science ®Google Scholar
• Finazzi G, Vannucchi AM, Martinelli V, et al. A phase II study of givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy. Br J Haematol 2013;161:688-94
   PubMed Web of Science ®Google Scholar
• Andersen CL, McMullin MF, Ejerblad E, et al. A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia. Br J Haematol 2013;162:498-508
   PubMed Web of Science ®Google Scholar
• Rambaldi A, Dellacasa CM, Finazzi G, et al. A pilot study of the histone-deacetylase inhibitor givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. Br J Haematol 2010;150:446-55
   PubMed Web of Science ®Google Scholar
• Pierce A, Spooncer E, Ainsworth S, et al. BCR-ABL alters the proliferation and differentiation response of multipotent hematopoietic cells to stem cell factor. Oncogene 2002;21:3068-75
   PubMed Web of Science ®Google Scholar
• Gaikwad A, Verstovsek S, Yoon D, et al. Imatinib effect on growth and signal transduction in polycythemia vera. Exp Hematol 2007;35:931-8
   PubMed Web of Science ®Google Scholar
• Merx K, Fabarius A, Erben P, et al. Effects of imatinib mesylate in patients with polycythemia vera: results of a phase II study. Ann Hematol 2013;92:907-15
   PubMed Web of Science ®Google Scholar
• A Study of LY2784544 in Participants With Myeloproliferative Neoplasms. Available from: https://clinicaltrials.gov/ct2/show/NCT01594723 [Last accessed 6 May 2015]
   Google Scholar
• Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia. Available from: www.clinicaltrials.gov/ct2/show/NCT01998828 [Last accessed 6 May 2015]
   Google Scholar
• Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF. Available from: www.clinicaltrials.gov/ct2/show/NCT02101268 [Last accessed 6 May 2015]
   Google Scholar
• RTT News. Sanofi Discontinues JAK2 Agent Fedratinib Clinical Trials - Quick Facts. Available at www.rttnews.com/2225631/sanofi-discontinues-jak2-agent-fedratinib-clinical-trials-quick-facts.aspx [Last accessed 6 May 2015
   Google Scholar
• Shi JG, Chen X, McGee RF, et al. The pharmacokinetics, pharmacodynamics, and safety of orally dosed INCB018424 phosphate in healthy volunteers. J Clin Pharmacol 2011;51:1644-54
   PubMed Web of Science ®Google Scholar
• JAKAVI® (ruxolitinib). Summary of Product Characteristics, Novartis, Horsham, West Sussex, United Kingdom. 2015
   Google Scholar
• JAKAVI® (ruxolitinib). Drug Monograph, Novartis, Dorval, Quebec, Canada. 2015
   Google Scholar
• Shi JG, Chen X, Emm T, et al. The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in healthy volunteers. J Clin Pharmacol 2012;52:809-18
   PubMed Web of Science ®Google Scholar
• Chen X, Shi JG, Emm T, et al. Pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in renal and hepatic impairment patients. Clin Pharmacol Drug Develop 2013;3:34-42
   PubMed Web of Science ®Google Scholar
• Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial). Available from: https://clinicaltrials.gov/ct2/show/NCT01243944 [Last accessed 6 May 2015]
   Google Scholar
• Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 2015;372:426-35
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Kiladjian JJ, Griesshammer M, et al. Results of a prospective, randomized, open-label phase 3 study of ruxolitinib (RUX) in polycythemia vera (PV) patients resistant to or intolerant of hydroxyurea (HU): the RESPONSE trial. Presented at: Annual Meeting of the American Society of Clinical Oncology; 2014. Chicago, IL; abstract 7026
   Google Scholar
• Randomized switch study from hydroxyurea to ruxolitinib for RELIEF of Polycythemia Vera symptoms: The Relief Study. Available from: https://clinicaltrials.gov/ct2/show/NCT01632904 [Last accessed 6 May 2015]
   Google Scholar
• Mesa R, Vannucchi AM, Yacoub A, et al. The Efficacy and Safety of Continued Hydroxyurea Therapy Versus Switching to Ruxolitinib in Patients with Polycythemia Vera: A Randomized, Double-Blind, Double-Dummy, Symptom Study (RELIEF). Blood (ASH Annual Meeting Abstracts) 2014. abstract 3168
   Google Scholar
• Ruxolitinib efficacy and safety in patients with hu resistant or intolerant Polycythemia Vera vs best available therapy. (RESPONSE 2). Available from: https://clinicaltrials.gov/ct2/show/NCT02038036 [Last accessed 6 May 2015]
   Google Scholar
• Sacchi S, Leoni P, Liberati M, et al. A prospective comparison between treatment with phlebotomy alone and with interferon-alpha in patients with polycythemia vera. Ann Hematol 1994;68:247-50
   PubMed Web of Science ®Google Scholar
• Silver RT. Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer 2006;107:451-8
   PubMed Web of Science ®Google Scholar
• Hasselbalch HC. A new era for IFN-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Expert Rev Hematol 2011;4:637-55
   PubMed Web of Science ®Google Scholar
• Gisslinger H, Buxhofer-Ausch V, Greil R, et al. Analysis of molecular responses and chromosomal aberrations in patients with polycythemia vera treated with peg-proline-interferon alpha-2b (AOP2014/P1101) in the Peginvera Study [abstract]. Blood 2013;122:1589
   Web of Science ®Google Scholar
• Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005;7:387-97
   PubMed Web of Science ®Google Scholar
• Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787-98
   PubMed Web of Science ®Google Scholar