Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

New England Journal of Medicine

Volumn 363, Issue 12, 2010, Pages 1117-1127

  Verstovsek, Srdan ^a   Kantarjian, Hagop ^a   Mesa, Ruben A ^b   Pardanani, Animesh D ^c   Cortes Franco, Jorge ^a   Thomas, Deborah A ^a   Estrov, Zeev ^a   Fridman, Jordan S ^d   Bradley, Edward C ^d   Erickson Viitanen, Susan ^d   Vaddi, Kris ^d   Levy, Richard ^d   Tefferi, Ayalew ^c  

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

^b MAYO CLINIC   (United States)

^c MAYO CLINIC   (United States)

^d NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BUSULFAN; INCB 018424; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE INHIBITOR; PEGINTERFERON; STAT3 PROTEIN; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; CYTOKINE; PYRAZOLE DERIVATIVE; RUXOLITINIB; STAT3 PROTEIN, HUMAN;

ADULT; AGED; ANEMIA; ANXIETY; ARTICLE; ASTHENIA; CLINICAL ARTICLE; CLINICAL TRIAL; DIARRHEA; DIZZINESS; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG MECHANISM; DRUG SAFETY; DYSPNEA; EDEMA; EPISTAXIS; FATIGUE; FEMALE; FEVER; FLATULENCE; GENE MUTATION; HEADACHE; HEART MURMUR; HUMAN; INSOMNIA; MALE; MULTIPLE CYCLE TREATMENT; MUSCULOSKELETAL PAIN; MYELOFIBROSIS; NAUSEA; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; POLYCYTHEMIA VERA; PRIORITY JOURNAL; SIDE EFFECT; THROMBOCYTOPENIA; THROMBOTIC THROMBOCYTOPENIC PURPURA; TREATMENT DURATION; TREATMENT RESPONSE; URINARY TRACT INFECTION; ANTAGONISTS AND INHIBITORS; BLOOD; COMPLICATION; DOSE RESPONSE; DRUG EFFECTS; GENETICS; HEPATOMEGALY; METABOLISM; MIDDLE AGED; MUTATION; PATHOLOGY; PRIMARY MYELOFIBROSIS; SPLEEN; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANEMIA; BIOLOGICAL MARKERS; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEPATOMEGALY; HUMANS; JANUS KINASE 1; JANUS KINASE 2; MALE; MIDDLE AGED; MUTATION; PRIMARY MYELOFIBROSIS; PYRAZOLES; SPLEEN; STAT3 TRANSCRIPTION FACTOR;

EID: 77956696835     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1002028     Document Type: Article

References (23)

1. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med 2000;342:1255-65.
2. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009;113:2895-901.
3. Cervantes F, Passamonti F, Barosi G. Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 2008;22:905-14. (Pubitemid 351698623)
4. 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;117:755-61.
5. Tefferi A. New insights into the pathogenesis and drug treatment of myelofibrosis. Curr Opin Hematol 2006;13:87-92. (Pubitemid 43755864)
6. 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.
7. Verstovsek S. Therapeutic potential of JAK2 inhibitors. Hematology Am Soc Hematol Educ Program 2009:636-42.
8. Barosi G, Bergamaschi G, Marchetti M, et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood 2007;110:4030-6.
9. Tefferi A, Lasho TL, Huang J, et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 2008;22:756-61. (Pubitemid 351559282)
10. Tefferi A, Lasho TL, Schwager SM, et al. The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005;131:320-8.
11. Williams DM, Kim AH, Rogers O, Spivak JL, Moliterno AR. Phenotypic variations and new mutations in JAK2 V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis. Exp Hematol 2007;35:1641-6. (Pubitemid 47633772)
12. Quintás-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.
13. Jaffe ES, Harris NL, Stein H, et al. World Health Organization classification of tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press, 2001.
14. Dupriez B, Morel P, Demory JL, et al. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 1996;88:1013-8. (Pubitemid 26333326)
15. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55.
16. Tefferi A, Barosi G, Mesa RA, et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood 2006;108:1497-503.
17. 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)
18. Mesa RA, Kantarjian H, Tefferi A, et al. Functional assessment of performance status in patients with myelofibrosis (MF): utility and feasibility of the 6-minute walk test (6MWT). J Clin Oncol 2009;27:Suppl:15S. abstract.
19. Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res 2009;33:1199-203.
20. Panteli KE, Hatzimichael EC, Bouranta PK, et al. Serum interleukin (IL)-1, IL-2, sIL-2Ra, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseases. Br J Haematol 2005;130:709-15.
21. Pajak B, Orzechowska S, Pijet B, et al. Crossroads of cytokine signaling - the chase to stop muscle cachexia. J Physiol Pharmacol 2008;59:Suppl 9:251-64.
22. Kurzrock R. The role of cytokines in cancer-related fatigue. Cancer 2001;92:Suppl:1684-8.
23. Guglielmelli P, Barosi G, Specchia G, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 2009;114:1477-83.