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2013, Número 1

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Rev Hematol Mex 2013; 14 (1)


Inhibición de JAK-2: su empleo en mielofibrosis y lecciones iniciales de la experiencia mexicana

Geyer HL, Tibes R, Mesa RA

Idioma: Ingles.
Referencias bibliográficas: 64
Paginas: 26-36
Archivo PDF: 640.91 Kb.


RESUMEN

Las neoplasias mieloproliferativas BCR-ABL negativas incluyen a la trombocitosis esencial o primaria, a la policitemia vera y a la mielofibrosis primaria. Este último padecimiento destaca por ser el de mayor morbilidad y mortalidad entre las subclases. El complejo biogenético subyacente a estas hemopatías clonales ha tenido, históricamente, avances notables en terapias contra genes específicos e inhibición de las citocinas proinflamatorias fundamentales para el inicio de los síntomas.
El descubrimiento de la mutación JAK2V617F condujo a la integración de biomarcadores genéticos para estrategias diagnósticas y terapéuticas. La década pasada quedó marcada por el desarrollo rápido de terapias con inhibidores de JAK2 capaces de reducir la esplenomegalia, las citopenias y los síntomas constitucionales con mínima mielosupresión y toxicidad secundaria.
El ruxolitinib fue el primer inhibidor JAK2 aprobado por la FDA en 2011 para riesgo alto e intermedio de mielofibrosis. El año pasado se realizaron avances notables en el entendimiento de eficacia, tolerabilidad y repercusiones en la esperanza de vida, incluido el análisis post-hoc de los ensayos COMFORT-I y COMFORT-II, la repercusión del fármaco a pesar de las trombocitopenias de base y efectos del estado mutacional de JAK2V617F. Sin embargo, la integración de los avances científicos en la práctica clínica permanece como un reto para todo el personal de salud que participa en el tratamiento de pacientes con mielofibrosis primaria.
El desarrollo reciente de los programas de abastecimiento individual de pacientes (Individual Patient Supply Programs) y los programas de uso compasivo (Compassionate Use Programs) se han extendido significativamente y las terapias eficaces a pacientes, que de otro modo no serían accesibles fuera del entorno de ensayos clínicos. Mientras se examina el futuro de los tratamientos de las neoplasias mieloproliferativas, está claro que la integración de los avances científicos debe permanecer paralela al tiempo-sensibilidad de la aplicación del paciente, para ofrecerle mayor alivio a quienes padecen alguna clase de neoplasia mieloproliferativa.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood 1951;6:372-375.

  2. Nowell PC. The minute chromosome (Phl) in chronic granulocytic leukemia. Blut 1962;8:65-66.

  3. 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.

  4. Ruiz-Arguelles GJ, Garces-Eisele J, Reyes-Nunez V, Ruiz- Delgado GJ, Navarro-Vazquez M, Gonzalez-Carrillo ML. The Janus Kinase 2 (JAK2) V617F mutation in hematological malignancies in Mexico. Rev Ibvest Clin Méx 2006;58:458-461.

  5. Ruiz-Arguelles GJ, Garces-Eisele J, Ortiz-Lopez R, Rivas- Llamas R, Gomez-Almaguer D, Ruiz-Delgado GJ. Molecular characterization of chronic myeloproliferative neoplasias in Mexico. Hematology 2009;14:261-265.

  6. 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;113:2895-2901.

  7. Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood 2005;105:973-977.

  8. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol 1999;61:10-15.

  9. Mesa R, Mehta J, Wang J, et al. Epidemiology of Myeloproliferative Disorders in US - a Real World Analysis. Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 2071.

  10. 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;30:4098-4103.

  11. Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol 2005;23:8520-8530.

  12. 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;22:437-438.

  13. Bain BJ, Clark DM, Lampert IA, Wilkens BS. Bone Marrow Pathology. 2nd ed. London: Blackwell Science, 2001.

  14. Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007;139:351-362.

  15. Della Porta MG, Malcovati L, Boveri E, et al. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol 2009;27:754- 762.

  16. Dekmezian R, Kantarjian HM, Keating MJ, Talpaz M, McCredie KB, Freireich EJ. The relevance of reticulin stain-measured fibrosis at diagnosis in chronic myelogenous leukemia. Cancer 1987;59:1739-1743.

  17. 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;111:1703-1708.

  18. 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;29:392-397.

  19. Kilpivaara O, Levine RL. JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia 2008;22:1813-1817.

  20. Trelinski J, Wierzbowska A, Krawczynska A, et al. Circulating endothelial cells in essential thrombocythemia and polycythemia vera: correlation with JAK2-V617F mutational status, angiogenic factors and coagulation activation markers. Int J Hematol 2011;91:792-798.

  21. Yu H, Jove R. The STATs of cancer--new molecular targets come of age. Nat Rev Cancer 2004;4:97-105.

  22. 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.

  23. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem 2005;280:22788- 22792.

  24. Jamal R, Belisle C, Lessard MC, et al. Evidence suggesting the presence of a stem cell clone anteceding the acquisition of the JAK2-V617F mutation. Leukemia 2008;22:1472-1474.

  25. Campbell PJ, Griesshammer M, Dohner K, et al. V617F mutation in JAK2 is associated with poorer survival in idiopathic myelofibrosis. Blood 2006;107:2098-2100.

  26. Vannucchi AM, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 2008;22:1299-1307.

  27. 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;110:4030-4036.

  28. 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- 1483.

  29. 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;115:3109-117.

  30. Verstovsek S KH, Pardanani AD, Thomas D, Cortes J, Mesa R, et al. The JAK inhibitor INCB018424 demonstrates durable and marked clinical reponses in primary myelofibrosis (PMF) and post-polycythemia/essential thrombocythemia myelofibrosis (post-PV/ET-MF). Blood 2008;112(suppl; abstr 1762).

  31. Verstovsek S KH, Estrov Z, Cortes J, Thomas D, Kadia T, Pierce S, et al. Comparison of Outcomes of Advanced Myelofibrosis Patients Treated with Ruxolitinib (INCB018424) to Those of a Historical Control Group: Survival Advantage of Ruxolitinib Therapy. Blood 2011;118:(suppl; abstr 793).

  32. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2011;366:787-98.

  33. 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: Abstract 800.

  34. Mesa R, Verstovsek S, Gupta V, et al. Improvement in Weight and Total Cholesterol and Their Association with Survival in Ruxolitinib- Treated Patients with Myelofibrosis From COMFORT-I. Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 1733.

  35. Vannucchi A, Passamonti F, Al-Ali 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 with Best Available Therapy (BAT). Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 802.

  36. 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: Abstract 801.

  37. Geyer HL, Cannon K, Knight E, et al. Ruxolitinib in Clinical Practice for Therapy of Myelofibrosis: Single USA Center Experience Following FDA Approval. ASE Annual Meeting Abstracts) 2012: Abstract 1749 2012.

  38. Nguyen H, Phram A, Perkins C, Linder A, Fechter L, Gotlib J. FDA-Approved Ruxolitinib in Patients with Myelofibrosis: the Stanford Experience. Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 1747.

  39. Talpaz M, Hamburg S, Jamieson K, et al. Preliminary safety and efficacy of ruxolitinib in patients (pts) with primary and secondary myelofibrosis (MF) with platelet counts (PC) of 50–100x109/L. J Clin Oncol 2012;30 (suppl; abstr 6630)

  40. Desterke C, Bilhou-Nabera C, Guerton B, et al. FLT3- mediated p38-MAPK activation participates in the control of megakaryopoiesis in primary myelofibrosis. Cancer research 2011;71:2901-2915.

  41. 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.

  42. Yuan ZL, Guan YJ, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005;307:269-273.

  43. Wang JC, Chen C, Dumlao T, et al. Enhanced histone deacetylase enzyme activity in primary myelofibrosis. Leuk Lymphoma 2008;49:2321-2327.

  44. Wang Y, Fiskus W, Chong DG, et al. Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells. Blood 2009;114:5024-5033.

  45. Baffert F, Evrot E, Ebel N, et al. Improved Efficacy Upon Combined JAK1/2 and Pan-Deacetylase Inhibition Using Ruxolitinib (INC424) and Panobinostat (LBH589) in Preclinical Mouse Models of JAK2V617F-Driven Disease. ASH Annual Meeting Abstracts 2011;118:798.

  46. 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;150:446-455.

  47. Barrio S, Gallardo M, Albizua E, et al. Epigenomic profiling in polycythaemia vera and essential thrombocythaemia shows low levels of aberrant DNA methylation. J Clin Pathol 2011;64:1010-1013.

  48. Teofili L, Martini M, Cenci T, et al. Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases. Int J Cancer 2008;123:1586-1592.

  49. Tibes RGF, McQueen T, Bergstrom DA, Freedman SJ, Andreeff M. Translational in vivo and in vitro studies in patients (pts) with acute myeloid leukemia (AML) chronic myeloid leukemia (CML) and myeloproliferative disease (MPD) treated with MK-0457 (MK), a novel aurora kinase, Flt3, JAK2, and Bcr-ABL inhibitor. Blood (ASH Annual Meeting Abstracts) 2006;108:1362.

  50. Barosi G, Agarwal M, Zweegman S, et al. An Individual Patient Supply Program for Ruxolitinib for the Treatment of Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF).

  51. Vargas P, Ovilla R, Alvarado R, et al. Compassionate Use Program (CUP) with Ruxolitinib in Mexican Patients with Primary Myelofibrosis (PMF), Post – Polycythemia, Vera Myelofibrosis (PPV – MF), and Post–Essential Thrombocythemia Myelofibrosis (PET – MF). Blood (ASH Annual Meeting Abstracts) 2012;120: Abstract 5067.

  52. Ruiz-Argüelles, Ruiz-Delgado, Galo-Hooker E, Sánchez-Sosa S. Ruxolitinib in chronic myelomonocytic leukemia-associated myelofibrosis: A case report. J Bione Marrow Res 2013; in the press

  53. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2011;363:1117-27.

  54. Mesa RA, Kantarjian H, Tefferi A, et al. Evaluating the serial use of the Myelofibrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Cancer 2010;117:4869-4877.

  55. Hexner E GJ, Prchal JT, Demakos EP, Swierczek S, Weinberg RS, Tripodi J. A multicenter, open label phase I/II study of CEP701(Lestaurtinib) in adults with myelofibrosis; a report on phase I: a study of the Myeloproliferative Disorders Research Consortium (MPD-RC). Blood 2009;114:(suppl; Abstr 754).

  56. Santos FP, Kantarjian HM, Jain N, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2008;115:1131-1136.

  57. Verstovsek S OO, Scott B, Estrov Z, Cortes J, Thomas DA, Wood J, Ethirajulu K, Low A, Zhu H, Kantarjian H, Deeg J. Phase I dose escalation trial of SB1518, a novel JAK2/FLT3 inhibitor, in acute and chronic myeloid diseases, including primary or post-essential thrombocythemia/polycythemia vera myelofibrosis. Blood 2009;114(suppl; abstr 3095).

  58. 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. ASH Annual Meeting Abstracts 2011;118:282-.

  59. Deeg H OO, Scott B, Estrov Z, Cortes J, Thomas D, Zhu H, Kantarjian H, Verstovsek S. Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis. J Clin Onc 2011;29;(suppl; abstr 6515).

  60. Komroji R, Wadleigh M, Seymour J, 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: Abstract 282.

  61. Shah NP OP, Sokol L, Verstovsek S, Hoffman R, List AF, Clary D, Bui L, Talpaz M. A phase I study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis. Blood 2008;112(suppl; abstr 98).

  62. Pardanani A, Gotlib JR, Jamieson C, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011;29:789-796.

  63. Verstovsek S, Mesa RA, Rhoades SK, et al. Phase I Study of the JAK2 V617F Inhibitor, LY2784544, in Patients with Myelofibrosis (MF), Polycythemia Vera (PV), and Essential Thrombocythemia (ET). ASH Annual Meeting Abstracts 2011;118:2814.

  64. Pardanini 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: Abstract 178.




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