Treatment and management of myelofibrosis in the era of JAK inhibitors

Biologics: Targets and Therapy

Volumn 7, Issue 1, 2013, Pages 189-198

  Keohane, Clodagh ^a   Radia, Deepti H ^a   Harrison, Claire N ^a  

^a GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

JAK inhibitor; Myelofibrosis; Ruxolitinib

Indexed keywords

ANTIANEMIC AGENT; BUPARLISIB; BUSULFAN; CLADRIBINE; DANAZOL; EVEROLIMUS; FEDRATINIB; HYDROXYUREA; JANUS KINASE; JANUS KINASE INHIBITOR; LENALIDOMIDE; MELPHALAN; MOMELOTINIB; PACRITINIB; PANOBINOSTAT; PEGINTERFERON; PLACEBO; POMALIDOMIDE; RUXOLITINIB; SONIDEGIB; THALIDOMIDE;

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANEMIA; BLOOD TRANSFUSION; BONE MARROW SUPPRESSION; CLINICAL FEATURE; CYTOPENIA; DIARRHEA; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG DOSE REDUCTION; DRUG MECHANISM; DRUG MEGADOSE; DRUG TOLERABILITY; EXTRAMEDULLARY HEMATOPOIESIS; FLUID RETENTION; HERPES ZOSTER; HIRSUTISM; HUMAN; IRRADIATION; LIBIDO; LIVER FUNCTION TEST; LIVER TUMOR; LOW DRUG DOSE; MULTIPLE CYCLE TREATMENT; MYELOFIBROSIS; MYELOPHTHISIC ANEMIA; NEUTROPENIA; PATHOGENESIS; POLYCYTHEMIA VERA; PROGNOSIS; PROTEIN TARGETING; PRURITUS; RADIATION DOSE FRACTIONATION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SPLENECTOMY; SPLENOMEGALY; SYMPTOM; THROMBOCYTHEMIA; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUBERCULOSIS;

EID: 84882793974     PISSN: 11775475     EISSN: 11775491     Source Type: Journal    
DOI: 10.2147/BTT.S34942     Document Type: Review

References (59)

1. Mesa R., Green A, Barosi G, Verstovsek S, Vardiman J, Gale RP. MPNassociated myelofibrosis (MPN-MF). Leuk Res. 2011;35(1):12-13.
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(13):2895-2901.
3. Barosi G, Rosti V, Vannucchi AM. Therapeutic approaches in myelofibrosis. Expert Opin Pharmacother. 2011;12(10):1597-1611.
4. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-1148.
5. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352(17):1779-1790.
6. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-1061.
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(4): 387-397.
8. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007; 356(5):459-468.
9. Oh ST, Simonds EF, Jones C, et al. Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood. 2010;116(6):988-992.
10. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.
11. Mesa R., 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.
12. Passamonti F, Cervantes F, Vannucchi AM, et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis Blood. 2010; 116(15):2857-2858.
13. Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9): 1703-1708.
14. Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29(4):392-397.
15. Vannucchi AM, Lasho TL, Guglielmelli P, et al. Mutations and prognosis in primary myelofibrosis. Leukemia. Epub April 26, 2013.
16. Jakafi (ruxolitinib) [package insert]. Wilmington, DE: Incyte Corporation; 2011.
17. 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(9):787-798.
18. Verstovsek S, Mesa R., Gotlib J, et al. A double-blind, placebocontrolled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9):799-807.
19. Verstovsek S, Passamonti F, Rambaldi A, et al. Long-term efficacy and safety results from a phase II study of ruxolitinib in patients with polycythemia vera. Blood (ASH Annual Meeting Abstracts). 2012; 120(21):804.
20. Cervantes F, Kiladjian J, 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). Blood (ASH Annual Meeting Abstracts). 2012;120(21):801.
21. Verstovsek S, Mesa R, Gotlib J, et al. Long-term outcome of ruxolitinib treatment in patients with myelofibrosis: durable reductions in spleen volume, improvements in quality of life, and overall survival advantage in COMFORT-I. Blood (ASH Annual Meeting Abstracts). 2012;120(21):800.
22. Kvasnicka HM, Thiele J, Bueso-Ramos C, et al. Long-term intervention effects on bone marrow morphology in myelofibrosis: Patients treated with ruxolitinib and best available therapy. Haematologica. 2013;98:Suppl 1:249 [abstract S591].
23. Kvasnicka HM, Thiele J, Bueso-Ramos C, et al. Exploratory analysis of the effect of ruxolitinib on bone marrow morphology in patients with myelofibrosis. J Clin Oncol, 2013 Annual Meeting Proc (Post-Meeting Edition). 2013;31 Suppl 15 (May 20 Suppl)[abstract 7030].
24. Vannucchi A, Kiladjian JJ, Gisslinger H, et al. Reductions in JAK2 V617F allele burden with ruxolitinib treatment in COMFORT-II, a phase 3 study comparing the safety and efficacy of ruxolitinib to best available therapy (BAT). Haematologica. 2012;97:Suppl 1:151 [abstract 0373].
25. Wernig G, Kharas MG, Okabe R, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell. 2008;13(4):311-320.
26. Talpaz M, Jamieson C, Gabrail N, et al. A phase II randomized doseranging study of the JAK2-selective inhibitor SAR302503 in patients with intermediate-2 or high-risk primary myelofibrosis (MF), postpolycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF. Blood (ASH Annual Meeting Abstracts). 2012;120(21):2837.
27. Pardanani A, Gotlib JR, Jamieson C, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol. 2011;29(7):789-796.
28. Pardanani A, Gotlib J, Gupta V, et al. Phase I/II study of CYT387, a JAK1/JAK2 inhibitor for the treatment of myelofibrosis. Blood (ASH Annual Meeting Abstracts). 2012;120(21):178.
29. Komrokji RS, Wadleigh M, Seymour JF, et al. Results of a phase 2 study of pacritinib (SB1518), a novel oral JAK2 inhibitor, in patients with primary, post-polycythemia vera, and post-essential thrombocythemia myelofibrosis. Blood (ASH Annual Meeting Abstracts). 2011; 118(21):282.
30. McLornan DP, Mead AJ, Jackson G, Harrison CN. Allogeneic stem cell transplantation for myelofibrosis in 2012. Br J Haematol. 2012;157(4): 413-425.
31. Mascarenhas J. Ruxolitinib Prior to Transplant in Patients With Myelofibrosis. Available from: http://clinicaltrials.gov/show/NCT01790295. Accessed July 29, 2013.
32. Martínez-Trillos A, Gaya A, Maffioli M, et al. Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol. 2010;89(12):1233-1237.
33. Faoro LN, Tefferi A, Mesa RA. Long-term analysis of the palliative benefit of 2-chlorodeoxyadenosine for myelofibrosis with myeloid metaplasia. Eur J Haematol. 2005;74(2):117-120.
34. Ianotto JC, Kiladjian JJ, Demory JL, et al. PEG-IFN-alpha-2a therapy in patients with myelofibrosis: a study of the French Groupe d'Etudes des Myelofibroses (GEM) and France Intergroupe des syndromes Myéloprolifératifs (FIM). Br J Haematol. 2009;146(2):223-225.
35. Mesa RA. How I treat symptomatic splenomegaly in patients with myelofibrosis. Blood. 2009;113(22):5394-5400.
36. Elliott MA, Tefferi A. Splenic irradiation in myelofibrosis with myeloid metaplasia: a review. Blood Rev. 1999;13(3):163-170.
37. Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, Sureda A, Torrebadell M, Montserrat E. Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature. Br J Haematol. 2004;127(4):399-403.
38. McMullin MF, Harrison CN, Niederwieser D, et al. The use of erythropoietic-stimulating agents (ESAs) with ruxolitinib in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), and post-essential thrombocythemia myelofibrosis (PETMF). Blood (ASH Annual Meeting Abstracts). 2012;120: (21):2838.
39. Kennedy BJ. Effect of androgenic hormone in myelofibrosis. JAMA. 1962;182:116-119.
40. Cervantes F, Alvarez-Larrán A, Domingo A, Arellano-Rodrigo E, Montserrat E. Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients. Br J Haematol. 2005;129(6):771-775.
41. Thapaliya P, Tefferi A, Pardanani A, et al. International working group for myelofibrosis research and treatment response assessment and longterm follow-up of 50 myelofibrosis patients treated with thalidomideprednisone based regimens. Am J Hematol. 2011;86(1):96-98.
42. Weinkove R, Reilly JT, McMullin MF, Curtin NJ, Radia D, Harrison CN. Low-dose thalidomide in myelofibrosis. Haematologica. 2008;93(7):1100-1101.
43. Tefferi A, Lasho TL, Mesa R., Pardanani A, Ketterling RP, Hanson CA. Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia. 2007;21(8): 1827-1828.
44. Shastri A, Cortes JE, Jabbour EJ, et al. A phase II study of low-dose pomalidomide (0.5 mg/day) and prednisone combination therapy in patients with myelofibrosis and significant anaemia. Blood (ASH Annual Meeting Abstracts). 2012;120(21):1728.
45. Begna KH, Mesa R., Pardanani A, et al. A phase-2 trial of low-dose pomalidomide in myelofibrosis. Leukemia. 2011;25(2):301-304.
46. Mesa R., Pardanani AD, Hussein K, et al. Phase 1/-2 study of pomalidomide in myelofibrosis. Am J Hematol. 2010;85(2):129-130.
47. Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anaemia associated with myelofibrosis. J Clin Oncol. 2009;27(27):4563-4569.
48. Tefferi A. Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2011;86(12):1017-1026.
49. Guglielmelli P, Barosi G, Rambaldi A, et al. Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis. Blood. 2011;118(8):2069-2076.
50. Vannucchi AM, Bogani C, Bartalucci N, et al. The mTOR inhibitor, RAD001, inhibits the growth of cells from patients with myeloproliferative neoplasms. Blood (ASH Annual Meeting Abstracts). 2009; 114(22):2914.
51. Vannucchi AM, Guglielmelli P, Lupo L, et al. A phase 1/2 study of RAD001, a mTOR inhibitor, in patients with myelofibrosis: final results. Blood (ASH Annual Meeting Abstracts). 2010;116(21):314.
52. Marks PA, Xu WS. Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem. 2009;107(4):600-608.
53. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5(9):769-784.
54. Mascarenhas J, Lu M, Li T, et al. A phase I study of panobinostat (LBH589) in patients with primary myelofibrosis (PMF) and postpolycythaemia vera/essential thrombocythaemia myelofibrosis (post-PV/ET MF). Br J Haematol. 2013;161(1):68-75.
55. DeAngelo DJ, Tefferi A, Fiskus W, et al. A phase II trial of panobinostat, an orally available deacetylase inhibitor, in patients with primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis. Blood (ASH Annual Meeting Abstracts). 2010;116(21):630.
56. Harrison C, Verstovsek S, McMullin MF, Mesa R. Janus kinase inhibition and its effect upon the therapeutic landscape for myelofibrosis: from palliation to cure? Br J Haematol. 2012;157(4):426-437.
57. Harrison CN, Kiladjian J, Passamonti F, et al. A phase 1b dosefinding study of ruxolitinib plus panobinostat in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Haematologica. 2012;97:Suppl 1:146 [abstract 0364].
58. Jakavi (ruxolitinib) [product monograph]. Dorval, QC: Novartis Pharmaceuticals Canada, Inc; 2012.
59. Mascarenhas J, Hoffman R.A, comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis. Blood. 2013;121(24):4832-4837.