Myelofibrosis: An update on current pharmacotherapy and future directions

Expert Opinion on Pharmacotherapy

Volumn 14, Issue 7, 2013, Pages 873-884

  Cervantes, Francisco ^a   Martinez Trillos, Alejandra ^b  

^a UNIVERSITY OF BARCELONA   (Spain)

^b INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

Author keywords

JAK2 inhibitors; Myelofibrosis; New drugs; Primary myelofibrosis; Treatment

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; AZACITIDINE; BUSULFAN; CLADRIBINE; DANAZOL; EVEROLIMUS; GANDOTINIB; GIVINOSTAT; HYDROXYUREA; JANUS KINASE 2; JANUS KINASE 3; LENALIDOMIDE; LESTAURTINIB; MELPHALAN; METANDIENONE; MOMELOTINIB; N TERT BUTYL 3 [5 METHYL 2 [4 [2 (1 PYRROLIDINYL)ETHOXY]PHENYLAMINO] 4 PYRIMIDINYLAMINO]BENZENESULFONAMIDE; NANDROLONE; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; OXYMETHOLONE; PACRITINIB; PANOBINOSTAT; POMALIDOMIDE; PREDNISONE; RUXOLITINIB; SARIDEGIB; THALIDOMIDE;

ACUTE LEUKEMIA; ALLOGENEIC STEM CELL TRANSPLANTATION; ANEMIA; BONE PAIN; CELL DIFFERENTIATION; CELL PROLIFERATION; CHRONIC MYELOID LEUKEMIA; CONSTIPATION; CYANOCOBALAMIN DEFICIENCY; DISEASE FREE SURVIVAL; DRUG WITHDRAWAL; EXTRAMEDULLARY HEMATOPOIESIS; FATIGUE; GENE MUTATION; GRAFT FAILURE; HEMATOLOGIC DISEASE; HEMATOPOIESIS; HEMOLYSIS; HEPATOMEGALY; HUMAN; INTERNATIONAL PROGNOSTIC SCORING SYSTEM; IRON DEFICIENCY; LIVER VEIN THROMBOSIS; LOW DRUG DOSE; MEGAKARYOCYTE; MYELOFIBROSIS; MYELOID METAPLASIA; MYELOPHTHISIC ANEMIA; MYELOPROLIFERATIVE DISORDER; PARESTHESIA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PORTAL HYPERTENSION; POSTOPERATIVE COMPLICATION; POSTOPERATIVE HEMORRHAGE; PROGNOSIS; PRURITUS; RADIATION INJURY; REVIEW; RNA SPLICING; SPLENOMEGALY; SURVIVAL; THROMBOCYTOPENIA; THROMBOCYTOSIS; TRANSPLANTATION;

AGE FACTORS; ANDROGENS; ANEMIA; HUMANS; IMMUNOLOGIC FACTORS; JANUS KINASE 2; MUTATION; PRIMARY MYELOFIBROSIS; PROGNOSIS; PYRAZOLES; RADIOTHERAPY; SPLENOMEGALY; STEM CELL TRANSPLANTATION; THALIDOMIDE;

EID: 84876065503     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2013.783019     Document Type: Review

References (80)

1. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007;110:1092-7
2. Mesa RA, Verstovsek S, Cervantes F, et al. Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): Consensus on terminology by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leuk Res 2007;31:737-40
3. Jacobson RJ, Salo A, Fialkow PJ. Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood 1978;51:189-94
4. Buschle M, Janssen JW, Drexler H, et al. Evidence of pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation. Leukemia 1988;2:658-60
5. Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol 1999;17:2954-70
6. Kralowics 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. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006;3:1140-51
8. Milosevic JD, Kralowics R. Genetic and epigenetic alterations of myeloproliferative disorders. Int J Hematol 2012; Epub ahead of print
9. Tefferi A, Lasho T, Jimma T, et al. One thousand patients with primary myelofibrosis: the Mayo Clinic experience. Mayo Clin Proc 2012;87:25-33
10. Tam CS, Nussenzveig RM, Popat U, et al. The natural history and treatment outcome of blast-phase BCR-ABL-negative myeloproliferative neoplasms. Blood 2008;112:1628-37
11. Cervantes F, Dupriez B, Pereira A, et al. A new prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009;113:2895-01
12. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Bone Marrow Transplant 2010;16:358-67
13. Cervantes F, Dupriez B, Passamonti F, et al. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol 2012;30:2981-7
14. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polychytemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005;7:387-97
15. Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 2011;29:573-82
16. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006;3:e270
17. Guglielmelli P, Biamonte F, Score J, et al. EZH2 mutational status predicts poor survival in myelofibrosis. Blood 2011;118:5227-34
18. Brecqueville M, Rey J, Bertucci F, et al. Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Gen Chromosome Cancer 2012;51:743-55
19. Abdel-Wahab O, Pardanani A, Bernard OA, et al. Unraveling rhe genetic underpinnings of myeloproliferative neoplasms and understanding their effect on disease course and response to therapy: proceedings from the 6th international post-ASH symposium. Am J Hematol 2012;87:562-8
20. Vannucchi A, Biamonte F. Epigenetics and mutations in chronic myeloproliferative neoplasms. Haematologica 2011;96:1398-402
21. Lasho TL, Jimma T, Finke CM, et al. SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. Blood 2012;120:4168-71
22. Wilkins BS, Erber WN, Bareford D, et al. Bone marrow pathology in essential thrombocythemia: inter-observer reliability and utility for identifying disease subtypes. Blood 2008;111:60-70
23. Buhr T, Hebeda K, Kaloutsi V, et al. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. Haematologica 2012;97:360-5
24. Barbui T, Thiele J, Passamonti F, et al. Survival and risk of leukemic transformation in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study of 1,104 patients. J Clin Oncol 2011;29:3179-84
25. Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 2008;22:437-8
26. Passamonti F, Cervantes F, Vannucchi A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the International Working Group for Myeloproliferative Neoplasms Research and Treatment. Blood 2010;115:1703-8
27. Gangat N, Pardanani A, Hanson CA, et al. DIPSS-Plus: a refined dynamic international prognostic scoring system (DIPSS) for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count and transfusion status. J Clin Oncol 2011;29:392-7
28. Martinez-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;89:1233-7
29. 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
30. Hast R, Engstedt L, Jameson S, et al. Oxymetholone treatment in myelofibrosis. Blut 1978;37:19-26
31. Brubaker LH, Briere J, Laszlo J, et al. Treatment of anemia in myeloproliferative disorders: a randomized study of fluoxymesterone v transfusions only. Arch Intern Med 1982;142:1533-7
32. Cervantes F, Alvarez-Larran A, Domingo A, et al. Efficacy and tolerability of danazol as a treatment for the anemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients. Br J Haematol 2005;129:771-5
33. Cervantes F, Alvarez-Larran A, Hernandez-Boluda JC, et al. Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature. Br J Haematol 2004;127:399-03
34. Cervantes F, Alvarez-Larran A, Hernandez-Boluda JC, et al. Efficacy and safety of darbepoetin-alpha in the anaemia of myelofibrosis with myeloid metaplasia. Br J Haematol 2006;134:184-6
35. Barosi G, Elliott M, Canepa M, et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from 5 studies. Leuk Lymph 2002;43:2301-7
36. Mesa RA, Steensma DP, Pardanani A, et al. A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood 2003;101:2534-41
37. Abgrall JF, Guibaud I, Bastie JN, et al. Thalidomide versus placebo in myeloid metaplasia with myelofibrosis: a prospective, randomized, double-blind, multicenter study. Haematologica 2006;91:1027-32
38. Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 2006;108:1158-64
39. Quintas-Cardama A, Kantarjian HM, Manshouri T, et al. Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol 2009;27:4760-6
40. Mesa RA, Yao X, Li CY, et al. Lenalidomide and prednisone for myelofibrosis: eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903. Blood 2010;116:4436-9
41. Oishi N, Swisher SN, Troup SB. Busulfan therapy in myeloid metaplasia. Blood 1960;15:863-72
42. Petti MC, Latagliata R, Spadea T, et al. Melphalan treatment in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 2002;116:576-81
43. Tefferi A, Silverstein MN, Li C-Y. 2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia. Br J Haematol 1997;99:352-7
44. Tefferi A, Mesa RA, Nagomey DN, et al. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 2000;95:2226-33
45. Lopez-Guillermo A, Cervantes F, Bruguera M, et al. Liver dysfunction following splenectomy in idiopathic myelofibrosis: a study of 10 patients. Acta Haematol 1991;85:184-8
46. Chaffanjon PC, Brichon PY, Ranchoup Y. Portal vein thrombosis following splenectomy for hematologic disease: retrospective study with Doppler color flow imaging. World J Surg 1998;22:1082-6
47. Bouabdallah R, Coso D, Gonzague-Casabianca L, et al. Safety and efficacy of splenic irradiation in the treatment of patients with idiopathic myelofibrosis: a report on 15 patients. Leuk Res 2000;24:491-5
48. Koeffler HP, Cline MJ, Golde DW. Splenic irradiation in myelofibrosis: effect on circulating myeloid progenitor cells. Br J Haematol 1979;43:69-77
49. Elliott MA, Chen MG, Silverstein MN, Tefferi A. Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia. Br J Haematol 1998;103:505-11
50. Barlett RP, Greipp PR, Tefferi A, et al. Extramedullary hematopoiesis manifesting as a symptomatic pleural effusion. Mayo Clin Proc 1995;70:1161-4
51. Steensma DP, Hook CC, Stafford SL, Tefferi A. Low-dose, single-fraction, whole-lung radiotherapy for pulmonary hypertension associated with myelofibrosis with myeloid metaplasia. Br J Haematol 2002;118:813-16
52. Guardiola P, Anderson JE, Bandini G, et al. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood 1999;93:2831-8
53. Guardiola P, Anderson JE, Gluckman E. Myelofibrosis with myeloid metaplasia (letter). N Engl J Med 2000;343:59
54. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Bone Marrow Transplant 2010;16:358-67
55. Scott BL, Gooley TA, Sorror ML, et al. The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood 2012;119:2657-64
56. Deeg HJ, Gooley TA, Flowers ME, et al. Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Blood 2003;102:3912-18
57. Cervantes F, Rovira M, Urbano-Ispizua A, et al. Remission of idiopathic myelofibrosis following donor lymphocyte infusion after failure of allogeneic stem cell transplantation. Bone Marrow Transplant 2000;26:697-9
58. Devine SM, Hoffman R, Verma A, et al. Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia. Blood 2002;99:2255-8
59. Kroger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 2009;114:5264-70
60. Alchalby H, Kroger N. Reduced-intensity conditioning followed by allogeneic hematopoietic stem cell transplantation in myelofibrosis. Curr Hematol Malig Rep 2010;5:53-61
61. Ditschowski M, Elmaagacli AH, Trenschel R, et al. Dynamic International Prognostic Scoring sytem scores, pre-transplant therapy and chronic gratf-versus-host disease determine outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. Haematologica 2012;97:1574-84
62. Santos FPS, Verstovsek S. JAK2 inhibitors: what's the true potential? Blood Rev 2011;25:53-63
63. Verstovsek S, Kantarjian HM, Mesa R, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117-27
64. 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
65. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib vs best available therapy in myelofibrosis. N Engl J Med 2012;366:787-98
66. Verstovsek S, Kantarjian HM, Estrov Z, et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood 2012;120:1202-9
67. Verstovsek S, Mesa RA, 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 2012;120:800
68. 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). Blood 2012;120:801
69. Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc 2011;86:1188-91
70. Tefferi A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood 2012;119:2721-30
71. Pardanani A, Gotlib JR, Jamieson C, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011;29:789-96
72. Pardanani AD, Caramazza D, George G, et al. Safety and efficacy of CYT387, a JAK 1/2 inhibitor, for the treatment of myelofibrosis. J Clin Oncol 2011;29(Suppl):abstract 6614
73. Pardanani A, Gotlib J, Gupta V, et al. Phase I/II study of CYT387, a JAK1/JAK2 inhibitor for the treatment of myelofibrosis. Blood 2012;120:178
74. Verstovsek S, Deeg HJ, Odenike O, et al. Phase 1-2 study of SB1518, a novel JAK2/FLT3 inhibitor, in the treatment of primary myelofibrosis. Blood 2010;116:3082
75. Santos FP, Kantarjian HM, Jain N, et al. Phase II study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2010;115:1131-6
76. Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 2009;27:4563-9
77. 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;118:2069-76
78. 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
79. De Angelo DJ, Tefferi A, Fiskus W, et al. A phase II trial of panobinostat, an orally available deacetylase inhibitor (DACi), in patients with primary myelofibrosis (PMF), post-essential thrombocythemia (ET), and post-polycythemia vera (PV) myelofibrosis. Blood 2010;116:630
80. Silver RT, Vandris K, Goldman JJ. Recombinant interferon-alpha may retard progression of early primary myelofibrosis: a preliminary report. Blood 2011;117:6669-72