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Vol 9, No 4 (2018)
Review paper
Published online: 2019-03-04

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Ruxolitinib in the treatment of patients with myelofibrosis — questions and answers

Krzysztof Warzocha1, Wojciech Homenda2, Andrzej Pluta3, Tomasz Sacha3, Maria Cioch4, Marek Dudziński5, Dorota Krochmalczyk6, Joanna Góra-Tybor1, Ilona Seferyńska1, Monika Joks7, Marta Sobas8
DOI: 10.5603/Hem.2018.0035
Hematologia 2018;9(4):269-284.

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References

  1. Homenda W, Hellmann A. Epidemiologia przewlekłych zespołów mieloproliferacyjnych w województwie słupskim w latach 1994–1998. Acta Haematol Pol. 2003; 34(4): 419–431.
  2. Chen X, Shi JG, Emm T, et al. Pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in renal and hepatic impairment patients. Clin Pharmacol Drug Dev. 2014; 3(1): 34–42.
    CrossRefPubMed
  3. Guglielmelli P, Vannucchi AM. Struggling with myelofibrosis-associated anemia. Leuk Res. 2013; 37(11): 1429–1431.
    CrossRefPubMed
  4. Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc. 2012; 87(1): 25–33.
    CrossRefPubMed
  5. Harrison C, Mesa R, Ross D, et al. Practical management of patients with myelofibrosis receiving ruxolitinib. Expert Rev Hematol. 2013; 6(5): 511–523.
    CrossRefPubMed
  6. Levine RL, Gilliland DG. Myeloproliferative disorders. Blood. 2008; 112(6): 2190–2198.
    CrossRefPubMed
  7. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9): 799–807.
    CrossRefPubMed
  8. Cervantes F, Vannucchi AM, Kiladjian JJ, et al. COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013; 122(25): 4047–4053.
    CrossRefPubMed
  9. Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, et al. Darbepoetin-alpha for the anaemia of myelofibrosis with myeloid metaplasia. Br J Haematol. 2006; 134(2): 184–186.
    CrossRefPubMed
  10. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015; 100(4): 479–488.
    CrossRefPubMed
  11. Huang J, Tefferi A. Erythropoiesis stimulating agents have limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis regardless of serum erythropoietin level. Eur J Haematol. 2009; 83(2): 154–155.
    CrossRefPubMed
  12. Anemia can be a challenge but usually does not preclude successful treatment. http://www.researchtopractice.com/Myelofibrosis14/Commentary4 (29.08.2018).
  13. Tsiara SN, Chaidos A, Bourantas LK, et al. Recombinant human erythropoietin for the treatment of anaemia in patients with chronic idiopathic myelofibrosis. Acta Haematol. 2007; 117(3): 156–161.
    CrossRefPubMed
  14. Cioch M, Jarosz P. Pierwotna mielofibroza — przegląd metod leczniczych. Acta Haematol Pol. 2014; 45(2): 143–148.
    CrossRef
  15. Gupta V, Harrison C, Hexner EO, et al. The impact of anemia on overall survival in patients with myelofibrosis treated with ruxolitinib in the COMFORT studies. Haematologica. 2016; 101(12): e482–e484.
    CrossRefPubMed
  16. Saeed I, McLornan D, Harrison CN. Managing side effects of JAK inhibitors for myelofibrosis in clinical practice. Expert Rev Hematol. 2017; 10(7): 617–625.
    CrossRefPubMed
  17. Mesa RA, Komrokji RS, Verstovsek S. Ruxolitinib dose management as a key to long-term treatment success. Int J Hematol. 2016; 104(4): 420–429.
    CrossRefPubMed
  18. Ikeda K, Ueda K, Sano T, et al. The amelioration of myelofibrosis with thrombocytopenia by a JAK1/2 inhibitor, ruxolitinib, in a post-polycythemia vera myelofibrosis patient with a JAK2 exon 12 mutation. Intern Med. 2017; 56(13): 1705–1710.
    CrossRefPubMed
  19. Al-Ali HK, Vannucchi AM. Managing patients with myelofibrosis and low platelet counts. Ann Hematol. 2017; 96(4): 537–548.
    CrossRefPubMed
  20. 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.
    CrossRefPubMed
  21. 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.
    CrossRefPubMed
  22. 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.
    CrossRefPubMed
  23. 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.
    CrossRefPubMed
  24. Manduzio P. Ruxolitinib in myelofibrosis: to be or not to be an immune disruptor. Ther Clin Risk Manag. 2017; 13: 169–177.
    CrossRefPubMed
  25. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015; 100(4): 479–488.
    CrossRefPubMed
  26. Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016; 30(8): 1701–1707.
    CrossRefPubMed
  27. Lussana F, Cattaneo M, Rambaldi A, et al. Ruxolitinib-associated infections: a systematic review and meta-analysis. Am J Hematol. 2018; 93(3): 339–347.
    CrossRefPubMed
  28. Heine A, Brossart P, Wolf D. Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective prophylaxis? Blood. 2013; 122(23): 3843–3844.
    CrossRefPubMed
  29. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9): 799–807.
    CrossRefPubMed
  30. 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.
    CrossRefPubMed
  31. Guglielmelli P, Rotunno G, Bogani C, et al. COMFORT-II Investigators. Ruxolitinib is an effective treatment for CALR-positive patients with myelofibrosis. Br J Haematol. 2016; 173(6): 938–940.
    CrossRefPubMed
  32. Guglielmelli P, Lasho TL, Rotunno G, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia. 2014; 28(9): 1804–1810.
    CrossRefPubMed
  33. Guglielmelli P, Biamonte F, Rotunno G, et al. COMFORT-II Investigators, Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative (AGIMM) Investigators. Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study. Blood. 2014; 123(14): 2157–2160.
    CrossRefPubMed
  34. Patel KP, Newberry KJ, Luthra R, et al. Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib. Blood. 2015; 126(6): 790–797.
    CrossRefPubMed
  35. Spiegel JY, McNamara C, Kennedy JA, et al. Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy. Blood Adv. 2017; 1(20): 1729–1738.
    CrossRefPubMed
  36. Sekhar M. Prevention and Management of Thrombosis in Myeloproliferative Neoplasms. Clin Adv Hematol Oncol. 2017; 15(3): 178–181.
  37. Devendra KC, Falchi L, Verstovsek S. The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review. Ann Hematol. 2017; 96(10): 1595–1604.
    CrossRefPubMed
  38. Barbui T, Finazzi G, Falanga A. Myeloproliferative neoplasms and thrombosis. Blood. 2013; 122(13): 2176–2184.
    CrossRefPubMed
  39. Falanga A, Marchetti M. Thrombotic disease in the myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program. 2012; 2012: 571–581.
    CrossRef
  40. Wolach O, Sellar RS, Martinod K, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci Transl Med. 2018; 10(436).
    CrossRefPubMed
  41. Samuelson BT, Vesely SK, Chai-Adisaksopha C, et al. The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood Coagul Fibrinolysis. 2016; 27(6): 648–652.
    CrossRefPubMed
  42. Pieri L, Paoli C, Arena U, et al. Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms. Am J Hematol. 2017; 92(2): 187–195.
    CrossRefPubMed
  43. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015; 372(5): 426–435.
    CrossRefPubMed
  44. Passamonti F, Griesshammer M, Palandri F, et al. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017; 18(1): 88–99.
    CrossRefPubMed
  45. Harrison CN, Mead AJ, Panchal A, et al. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017; 130(17): 1889–1897.
    CrossRefPubMed
  46. Verstovsek S, Passamonti F, Rambaldi A, et al. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017; 130(15): 1768–1771.
    CrossRefPubMed
  47. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016; 91(12): 1262–1271.
    CrossRefPubMed
  48. Mesa RA, Passamonti F. Individualizing Care for Patients With Myeloproliferative Neoplasms: Integrating Genetics, Evolving Therapies, and Patient-Specific Disease Burden. Am Soc Clin Oncol Educ Book. 2016; 35: e324–e335.
    CrossRefPubMed
  49. Newberry KJ, Patel K, Masarova L, et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017; 130(9): 1125–1131.
    CrossRefPubMed
  50. Coltro G, Mannelli F, Guglielmelli P, et al. A life-threatening ruxolitinib discontinuation syndrome. Am J Hematol. 2017; 92(8): 833–838.
    CrossRefPubMed
  51. Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc. 2011; 86(12): 1188–1191.
    CrossRefPubMed
  52. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9): 799–807.
    CrossRefPubMed
  53. Dai T, Friedman EW, Barta SK. Ruxolitinib withdrawal syndrome leading to tumor lysis. J Clin Oncol. 2013; 31(29): e430–e432.
    CrossRefPubMed
  54. Beauverd Y, Samii K. Acute respiratory distress syndrome in a patient with primary myelofibrosis after ruxolitinib treatment discontinuation. Int J Hematol. 2014; 100(5): 498–501.
    CrossRefPubMed
  55. Herman DD, Kempe CB, Thomson CC, et al. Recurrent hypoxemic respiratory failure. Beyond the usual suspects. Ann Am Thorac Soc. 2014; 11(7): 1145–1148.
    CrossRefPubMed
  56. Tefferi A, Wassie EA, Lasho TL, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014; 28(7): 1472–1477.
    CrossRefPubMed
  57. 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.
    CrossRefPubMed
  58. 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.
    CrossRefPubMed
  59. 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.
    CrossRefPubMed
  60. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017; 10(1): 55.
    CrossRefPubMed
  61. Kuykendall AT, Talati C, Al Ali N, et al. The Treatment Landscape of Myelofibrosis Before and After Ruxolitinib Approval. Clin Lymphoma Myeloma Leuk. 2017; 17(12): e45–e53.
    CrossRefPubMed
  62. Caocci G, Ghiani S, Mocci C, et al. Combination Therapy with Ruxolitinib and Hydroxyurea for the Treatment of Myeloid-Predominant Leukocytosis in a Patient with Myelofibrosis. Acta Haematol. 2018; 139(3): 164–165.
    CrossRefPubMed
  63. Cerchione C, Peluso I, Nappi D, et al. Ruxolitinib rechallenge in combination with hydroxyurea is effective in reverting cachexia and reducing blood transfusion demand and splenomegaly symptoms in a patient with primary myelofibrosis. Ann Hematol. 2017; 96(4): 697–699.
    CrossRefPubMed
  64. Mesa RA, Schwager S, Huang J, et al. Weight loss, splenomegaly, and hypocholesterolemia in myeloproliferative neoplasms: patterns and relevance from the pre JAK2 inhibitor era [abstract]. Blood. 2009; 114(22): 3918.
  65. Mesa RA, Huang J, Schwager S, et al. Hypocholesterolemia is independently associated with decreased survival in patients with primary myelofibrosis: an analysis of lipid profiles in 558 myeloproliferative patients [abstract]. Blood. 2007; 110(11): 2548.
  66. Sulai N, Mengistu B, Gangat N, et al. Decreased levels of total or HDL cholesterol in primary myelofibrosis are associated with shortened survival: DIPSS-Plus independent prognostic value [abstract]. Blood. 2012; 120(21): 2851.
  67. 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.
    CrossRefPubMed
  68. 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.
    CrossRefPubMed
  69. Mesa RA, Verstovsek S, Gupta V, et al. Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. Clin Lymphoma Myeloma Leuk. 2015; 15(4): 214–221.e1.
    CrossRefPubMed
  70. Argiles JM, Lopez-Soriano FJ, Busquets S. Counteracting inflammation: a promising therapy in cachexia. Crit Rev Oncog. 2012; 17(3): 253–262.
    CrossRefPubMed
  71. Fearon KCH, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012; 16(2): 153–166.
    CrossRefPubMed
  72. Tefferi A, Vaidya R, Caramazza D, et al. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol. 2011; 29(10): 1356–1363.
    CrossRefPubMed
  73. Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc. 2012; 87(1): 25–33.
    CrossRefPubMed
  74. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators, COMFORT Investigators, COMFORT-I investigators. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010; 363(12): 1117–1127.
    CrossRefPubMed
  75. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9): 799–807.
    CrossRefPubMed
  76. Tefferi A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood. 2012; 119(12): 2721–2730.
    CrossRefPubMed
  77. 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.
    CrossRefPubMed

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