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Review

Emerging drugs for the treatment of Myelofibrosis

&
Pages 37-49 | Received 18 Dec 2017, Accepted 22 Feb 2018, Published online: 06 Mar 2018

References

  • Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405.
  • Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(12):1262–1271.
  • Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med. 2000;342(17):1255–1265.
  • Mehta J, Wang H, Iqbal SU, et al. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma. 2014;55(3):595–600.
  • 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.
  • 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.
  • Cervantes F, Dupriez B, Passamonti F, et al. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol. 2012;30(24):2981–2987.
  • Cervantes F, Pereira A. Does ruxolitinib prolong the survival of patients with myelofibrosis? Blood. 2017;129(7):832–837.
  • Mesa RA, Li C-Y, Ketterling RP, et al. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood. 2005;105(3):973–977.
  • Deisseroth A, Kaminskas E, Grillo J, et al. U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212–3217.
  • Mascarenhas JO, Orazi A, Bhalla KN, et al. Advances in myelofibrosis: a clinical case approach. Haematologica. 2013;98(10):1499–1509.
  • Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472–1477.
  • 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.
  • 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.
  • 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.
  • 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.
  • Lu X, Huang LJ, Lodish HF. Dimerization by a cytokine receptor is necessary for constitutive activation of JAK2V617F. J Biol Chem. 2008;283(9):5258–5266.
  • 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.
  • Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–2405.
  • Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–2390.
  • Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010;24(6):1128–1138.
  • Tefferi A, Finke CM, Lasho TL, et al. U2AF1 mutations in primary myelofibrosis are strongly associated with anemia and thrombocytopenia despite clustering with JAK2V617F and normal karyotype. Leukemia. 2014;28(2):431–433.
  • 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.
  • Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395–1398.
  • 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(33):4098–4103.
  • Cervantes F, Isola IM, Alvarez-Larrán A, et al. Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results. Ann Hematol. 2015;94(11):1791–1796.
  • Cervantes F, Alvarez-Larrán A, Hernández-Boluda J-C, 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(4):399–403.
  • Verstovsek, S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.
  • Harrison, C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–798.
  • Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363(12):1117–1127.
  • Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156.
  • Abgrall J-F, Guibaud I, Bastie J-N, et al. Thalidomide versus placebo in myeloid metaplasia with myelofibrosis: a prospective, randomized, double-blind, multicenter study. Haematologica. 2006;91(8):1027–1032.
  • Mesa RA, Elliott MA, Schroeder G, et al. Durable responses to thalidomide-based drug therapy for myelofibrosis with myeloid metaplasia. Mayo Clin Proc. 2004;79(7):883–889.
  • Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. 2006;108(4):1158–1164.
  • Jabbour E, Thomas D, Kantarjian H, et al. Comparison of thalidomide and lenalidomide as therapy for myelofibrosis. Blood. 2011;118(4):899–902.
  • Quintás-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(28):4760–4766.
  • Mesa RA, Pardanani AD, Hussein K, et al. Phase1/-2 study of Pomalidomide in myelofibrosis. Am J Hematol. 2010;85(2):129–130.
  • Begna KH, Mesa RA, Pardanani A, et al. A phase-2 trial of low-dose pomalidomide in myelofibrosis. Leukemia. 2011;25(2):301–304.
  • Tefferi A, Al-Ali HK, Barosi G, et al. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia. 2017;31(4):896–902.
  • Kroger N. Outcome improvement after allogeneic stem-cell transplantation in myelofibrosis. J Oncol Pract. 2016;12(7):629–631.
  • Kroger, N, Giorgino T, Scott BL, et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood. 2015;125(21):3347–50; quiz 3364.
  • 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(26):5264–5270.
  • Rondelli D, Goldberg JD, Isola L, et al. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2014;124(7):1183–1191.
  • Hanif A, Hari PN, Atallah E, et al. Safety of ruxolitinib therapy prior to allogeneic hematopoietic stem-cell transplantation for myeloproliferative neoplasms. Bone Marrow Transplant. 2016;51(4):617–618.
  • Gupta V,Kosiorek H, Klisovic R et al. Exploring the potential of JAK1/2 inhibitor ruxolitinib with reduced intensity hematopoietic cell transplantation (HCT) for myelofibrosis: stage I results of a prospective trial conducted through the Myeloproliferative Disorders - Research Consortium (MPD-RC). Blood. 2016.128:1126
  • Kuzanar W. American health and drug benefits : cost of treating patients with ruxolitinib. Health Econ. 2013;6(No.1 special issue). Available from: http://www.ahdbonline.com/issues/2013/february-2013-vol-6-no-1-special-issue/1289-article-1289
  • Beggs J. Myelofibrosis market will exceed $1 billion by 2025, says GlobalData. Chem Cures. 2016. Available from: http://www.chemdiv.com/myelofibrosis-market-will-exceed-1-billion-2025-says-globaldata/
  • Pardanani A, Laborde RR, Lasho TL, et al. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia. 2013;27(6):1322–1327.
  • Mesa RA, Kiladjian -J-J, Catalano JV, et al. Simplify-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus Kinase Inhibitor–Naïve Patients With Myelofibrosis. J Clin Oncol. 2017;35(34):3844–3850.
  • Harrison, CN, Vannucchi AM, Platzbecker U, et al. Phase 3 randomized trial of momelotinib (MMB) versus best available therapy (BAT) in patients with myelofibrosis (MF) previously treated with ruxolitinib (RUX). DOI: 10.1200/JCO.2017.35.15_suppl.7001. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 7001-7001.
  • Verstovsek S, Odenike O, Singer JW, et al. Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. J Hematol Oncol. 2016;9(1):137.
  • Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017;4(5):e225–e236.
  • Mascarenhas J,Hoffman R, Talpaz M, et al. Results of the Persist-2 phase 3 study of pacritinib (PAC) versus best available therapy (BAT), including ruxolitinib (RUX), in patients (pts) with myelofibrosis (MF) and platelet counts< 100,000/µl. Blood. 2016;128:LBA–5.
  • 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(24):5024–5033.
  • Glaser KB. HDAC inhibitors: clinical update and mechanism-based potential. Biochem Pharmacol. 2007;74(5):659–671.
  • Mascarenhas J, Sandy L, Lu M, et al. A phase II study of panobinostat in patients with primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF). Leuk Res. 2017;53:13–19.
  • Harrison CN, Kiladjian J, Heidel F, et al. Efficacy, safety, and confirmation of the recommended phase 2 starting dose of the combination of Ruxolitinib (RUX) and Panobinostat (PAN) in Patients (Pts) with Myelofibrosis (MF). Blood. 2015;126(23):4060–4061.
  • Ribrag VT. A Phase 1b, dose-finding study of ruxolitinib plus panobinostat in patients with Primary Myelofibrosis (PMF), Post–polycythemia Vera MF (PPV-MF), or post–essential thrombocythemia MF (PET-MF): identification of the recommended Phase 2 dose. Blood. 2013;122:4045.
  • Andersen CL, Mortensen NB, Klausen TW, et al. A phase II study of vorinostat (MK-0683) in patients with primary myelofibrosis and post-polycythemia vera myelofibrosis. Haematologica. 2014;99(1):e5–7.
  • Quintás-Cardama A, Kantarjian H, Estrov Z, et al. Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis. Leuk Res. 2012;36(9):1124–1127.
  • Quintás-Cardama A, Tong W, Kantarjian H, et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia. 2008;22(5):965–970.
  • Odenike OM, Godwin JE, van Besien K, et al. Phase II study of decitabine in myelofibrosis with myeloid metaplasia. Blood. 2006;108:4923.
  • DaverN, Cortez J, Pemmaraju N, et al. Ruxolitinib (RUX) in combination with 5-azacytidine (AZA) as therapy for patients (pts) with myelofibrosis (MF). Blood. 2016;128:1127. American Society of Hematology.
  • RampalR,Mascarenhas J, Kosiorek H, et al. Safety and efficacy of combined ruxolitinib and decitabine in patients with blast-phase MPN and post-MPN AML: results of a Phase I Study (Myeloproliferative Disorders Research Consortium 109 trial). Blood. 2016;128:1127. American Society of Hematology.
  • XuN, Li Y, Zhou X, et al. LOXL2 highly-expressed induce the transition of stromal cells into cancer-associated fibroblasts which maybe involve in myeloproliferative neoplasms progession. Blood. 2015;126:5207. American Society of Hematology.
  • Mascarenhas J, Li T, Sandy L, et al. Anti-transforming growth factor-beta therapy in patients with myelofibrosis. Leuk Lymphoma. 2014;55(2):450–452.
  • Bose P, Daver N, Jabbour E, et al. Phase-2 study of sotatercept (ACE-011) in myeloproliferative neoplasm-associated myelofibrosis and anemia. Blood. 2016;128:478. American Society of Hematology.
  • VerstovsekS, Mesa R, Foltz L, et al. PRM-151 in myelofibrosis: durable efficacy and safety at 72 weeks. Blood. 2015;126:56. American Society of Hematology.
  • Duffield JS, Lupher ML. PRM-151 (recombinant human serum amyloid P/pentraxin 2) for the treatment of fibrosis. Drug News Perspect. 2010;23(5):305–315.
  • VerstovsekS, Mesa R, Foltz L, et al. Phase 2 trial of PRM-151, an anti-fibrotic agent, in patients with myelofibrosis: stage 1 results. Blood. 2014;124:713. American Society of Hematology.
  • Frankel A, Woo J, Ahn C, et al. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients.
  • Lasho T, Finke C, Kimlinger T, et al. Expression of CD123 (IL-3R-alpha), a Therapeutic Target of SL-401, on Myeloproliferative Neoplasms. Blood. 2014;124:5577. American Society of Hematology.
  • Patnaik MM, Gupta V, Gotlib J, et al. Results from ongoing phase 2 trial of SL-401 in patients with advanced, high-risk myeloproliferative neoplasms including chronic myelomonocytic leukemia. Blood. 2016;128:4245. American Society of Hematology.
  • Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol. 2006;6(11):836–848.
  • Lu M, Zhang W, Li Y, et al. Interferon-alpha targets JAK2V617F-positive hematopoietic progenitor cells and acts through the p38 MAPK pathway. Exp Hematol. 2010;38(6):472–480.
  • Silver RT. Recombinant interferon-alpha for treatment of polycythaemia vera. Lancet. 1988;2(8607):403.
  • Silver RT, Vandris K. Recombinant interferon alpha (rIFN alpha-2b) may retard progression of early primary myelofibrosis. Leukemia. 2009;23(7):1366–1369.
  • IanottoJC, Kiladjian J, Demory J, 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 Myeloproliferatifs (FIM). Br J Haematol. 2009;146(2):223–225.
  • Mikkelsen SU, Kjor L, Skov V, et al. Safety and efficacy of combination therapy of interferon-Alpha2 + JAK1-2 inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the Danish Combi-Trial - an open label, single arm, non-randomized multicenter Phase II study. Am Soc Hematol. 2015.
  • Bernard L, Belisle C, Mollica L et al. Telomere length is severely and similarly reduced in jak2v617f-positive and -negative myeloproliferative neoplasms. Leukemia. 2009;23(2):287–291.
  • Tefferi A, Lasho TL, Begna KH, et al. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Engl J Med. 2015;373(10):908–919.
  • Pemmaraju N, Carter B, Kantarjian H, et al. Results for phase II clinical trial of LCL161, a SMAC mimetic, in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF) or post-essential thrombocytosis myelofibrosis (post-ET MF). Blood. 2016;128:3105. American Society of Hematology.
  • Gupta V, Harrison C, Hasselbalch H, et al. Phase 1b/2 study of the efficacy and safety of sonidegib (LDE225) in combination with ruxolitinib (INC424) in patients with myelofibrosis. Blood. 2015;126:825. American Society of Hematology.
  • Pinton L, Solito S, Damuzzo V, et al. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression. Oncotarget. 2016;7(2):1168–1184.
  • Daver N, Basu S, Garcia M, et al. Defining the immune checkpoint landscape in patients with acute myeloid leukemia. Blood. 2016;128:2900.
  • Tefferi A, Lasho TL, Finke CM, et al. Targeted deep sequencing in primary myelofibrosis. Blood Adv. 2016;1(2):105–111.
  • Tefferi A, Guglielmelli P, Lasho TL, et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia. 2014;28(7):1494–1500.
  • Tefferi A, Guglielmelli P, Finke C, et al. Integration of mutations and karyotype towards a genetics-based prognostic scoring system (GPSS) for primary myelofibrosis. Blood. 2014;124(21):406.
  • Vannucchi AM, Guglielmelli P, Rotunno G, et al. Mutation-enhanced international prognostic scoring system (MIPSS) for primary myelofibrosis: an AGIMM & IWG-MRT Project. Blood. 2014;124(21):405.
  • MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2017;JCO2017764886.

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