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

Volumn 120, Issue 4, 2014, Pages 513-520

  Verstovsek, Srdan ^a,i   Passamonti, Francesco ^b   Rambaldi, Alessandro ^c   Barosi, Giovanni ^d   Rosen, Peter J ^e   Rumi, Elisa ^d   Gattoni, Elisabetta ^f   Pieri, Lisa ^g   Guglielmelli, Paola ^g   Elena, Chiara ^d   He, Shui ^h   Contel, Nancy ^h   Mookerjee, Bijoyesh ^h   Sandor, Victor ^h   Cazzola, Mario ^d   Kantarjian, Hagop M ^a   Barbui, Tiziano ^c   Vannucchi, Alessandro M ^g  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b Division of Hematology   (Italy)

^c Azienda Ospedaliera Papa Giovanni XXIII   (Italy)

^d FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^e Tower Cancer Research Foundation ^*  (United States)

^f Ospedale S Spirito Casale Monferrato   (Italy)

^g UNIVERSITY OF FLORENCE   (Italy)

^h Experimental Station   (United States)

ⁱ UNIVERSITY OF PAVIA   (Italy)

Author keywords

Janus kinase (JAK) inhibitor; myeloproliferative neoplasm; phase 2; polycythemia vera; ruxolitinib

Indexed keywords

ADULT; AGED; AGED, 80 AND OVER; ANEMIA; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; FEMALE; GRANULOCYTES; HEMATOCRIT; HUMANS; HYDROXYUREA; JANUS KINASE 1; JANUS KINASE 2; MALE; MIDDLE AGED; POLYCYTHEMIA VERA; PYRAZOLES; THROMBOCYTOPENIA; YOUNG ADULT;

EID: 84893733177     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.28441     Document Type: Article

References (31)

1. Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004; 117: 755-761. (Pubitemid 39482529)
2. Barbui T, Barosi G, Birgegard G, et al. European LeukemiaNet. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011; 29: 761-770.
3. Tefferi A,. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012; 87: 285-293.
4. 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: 401-408.
5. Silver RT,. Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer. 2006; 107: 451-458. (Pubitemid 44107203)
6. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365: 1054-1061. (Pubitemid 40386783)
7. 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: 387-397. (Pubitemid 40544655)
8. Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A,. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007; 21: 1960-1963. (Pubitemid 47299970)
9. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007; 356: 459-468. (Pubitemid 46193073)
10. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366: 799-807.
11. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010; 363: 1117-1127.
12. 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: 787-798.
13. 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: 3109-3117.
14. Tefferi A, Vardiman JW,. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008; 22: 14-22.
15. 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: 961-963.
16. Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009; 113: 4829-4833.
17. 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: 4778-4781.
18. National Cancer Institute Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. ctep.cancer.gov/protocolDevelopment/electronic-applications/docs/ctcaev3.pdf. Accessed August 15, 2013.
19. Hillman SL, Mandrekar SJ, Bot B, et al. Evaluation of the value of attribution in the interpretation of adverse event data: a North Central Cancer Treatment Group and American College of Surgeons Oncology Group investigation. J Clin Oncol. 2010; 28: 3002-3007.
20. 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: 5418-5424.
21. 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: 3065-3072.
22. Turlure P,. Complete hematological, molecular and histological remissions without cytoreductive treatment lasting after pegylated-interferon α-2a (peg-IFNα-2a) therapy in polycythemia vera (PV): long term results of a phase 2 trial [abstract]. Presented in abstract form at: American Society of Hematology Annual Meeting and Exposition; December 10-12, 2011; San Diego, CA. Abstract 280.
23. 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. (Pubitemid 46120195)
24. 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: 2224-2232. (Pubitemid 46218714)
25. 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: 1574-1579.
26. 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.
27. Passamonti F, Rumi E, Caramella M, et al. A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis. Blood. 2008; 111: 3383-3387.
28. Landolfi R, Di Gennaro L, Barbui T, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007; 109: 2446-2452. (Pubitemid 46425887)
29. Abdulkarim K, Ridell B, Johansson P, Kutti J, Safai-Kutti S, Andreasson B,. The impact of peripheral blood values and bone marrow findings on prognosis for patients with essential thrombocythemia and polycythemia vera. Eur J Haematol. 2011; 86: 148-155.
30. Verstovsek S, Mesa RA, Gotlib J, et al. Efficacy, safety, and survival with ruxolitinib treatment in patients with myelofibrosis results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013 Sept 13. Epub ahead of print. PMID 24038026.
31. Cervantes F, Kiladjian JJ, Niederwieser D, et al. Long-term safety, efficacy, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy (BAT) for the treatment of myelofibrosis (MF). Presented in abstract form at: American Society of Hematology Annual Meeting and Exposition; December 8-11, 2012; Atlanta, GA. Abstract 801.