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Thrombocytopenia in patients with myelofibrosis: management options in the era of JAK inhibitor therapy

ORCID Icon, , , &
Pages 1535-1547 | Received 18 Nov 2019, Accepted 03 Feb 2020, Published online: 24 Feb 2020

References

  • Reilly JT, McMullin MF, Beer PA, et al. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol. 2012;158(4):453–471.
  • Rumi E, Pietra D, Pascutto C, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062–1069.
  • Passamonti F, Mora B, Giorgino T, et al. Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients. Leukemia. 2017;31(4):970–973.
  • Pecquet C, Chachoua I, Roy A, et al. Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants. Blood. 2019;133(25):2669–2681.
  • Guglielmelli P, Lasho TL, Rotunno G, et al. MIPSS70: Mutation-Enhanced International Prognostic Score System for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2018;36(4):310–318.
  • Rampal R, Al-Shahrour F, Abdel-Wahab O, et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood. 2014;123(22):e123–133.
  • Tefferi A, Finke CM, Lasho TL, et al. U2AF1 mutation types in primary myelofibrosis: phenotypic and prognostic distinctions. Leukemia. 2018;32(10):2274–2278.
  • 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.
  • 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.
  • 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.
  • Passamonti F, Giorgino T, Mora B, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31(12):2726–2731.
  • Tefferi A, Guglielmelli P, Lasho TL, et al. MIPSS70+ version 2.0: mutation and karyotype-enhanced International Prognostic Scoring System for primary myelofibrosis. J Clin Oncol. 2018;36(17):1769–1770.
  • 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.
  • Cervantes F, Alvarez-Larran A, Domingo A, et al. 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.
  • Crisa E, Cilloni D, Elli EM, et al. The use of erythropoiesis-stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib. Br J Haematol. 2018;182(5):701–704.
  • 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(7):2534–2541.
  • 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.
  • Gerds AT, Vannucchi AM, Passamonti F, et al. A phase 2 study of luspatercept in patients with myelofibrosis-associated anemia. Blood. 2019;134(Suppl. 1):557.
  • 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.
  • Hernández-Boluda JC, Pereira A, Gomez M, et al. The International Prognostic Scoring System does not accurately discriminate different risk categories in patients with post-essential thrombocythemia and post-polycythemia vera myelofibrosis. Haematologica. 2014;99(4):e55–e57.
  • Masarova L, Alhuraiji A, Bose P, et al. Significance of thrombocytopenia in patients with primary and postessential thrombocythemia/polycythemia vera myelofibrosis. Eur J Haematol. 2018;100(3):257–263.
  • Hernández-Boluda JC, Pereira A, Correa JG, et al. Performance of the myelofibrosis secondary to PV and ET-prognostic model (MYSEC-PM) in a series of 262 patients from the Spanish registry of myelofibrosis. Leukemia. 2018;32(2):553–555.
  • Kander EM, Raza S, Zhou Z, et al. Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort. Int J Hematol. 2015;102(5):587–593.
  • Barkhan P. Blood and neoplastic diseases. Thrombocytopenia. Br Med J. 1974;2(5914):324–325.
  • Mughal TI, Vaddi K, Sarlis NJ, et al. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. Int J Gen Med. 2014;7:89–101.
  • Boruchov AM. Thrombocytopenia in myelodysplastic syndromes and myelofibrosis. Semin Hematol. 2009;46(1 Suppl 2):S37–S43.
  • Smock KJ, Perkins SL. Thrombocytopenia: an update. Int Jnl Lab Hem. 2014;36(3):269–278.
  • Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–2513.
  • 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(12):1233–1237.
  • 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 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.
  • Palandri F, Tiribelli M, Benevolo G, et al. Efficacy and safety of ruxolitinib in intermediate-1 IPSS risk myelofibrosis patients: results from an independent study. Hematol Oncol. 2018;36(1):285–290.
  • Newberry KJ, Patel K, Masarova L, et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017;130(9):1125–1131.
  • Patnaik MM, Caramazza D, Gangat N, et al. Age and platelet count are IPSS-independent prognostic factors in young patients with primary myelofibrosis and complement IPSS in predicting very long or very short survival. Eur J Haematol. 2010;84(2):105–108.
  • Tam CS, Kantarjian H, Cortes J, et al. Dynamic model for predicting death within 12 months in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. J Clin Oncol. 2009;27(33):5587–5593.
  • Gagelmann N, Ditschkowski M, Bogdanov R, et al. Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood. 2019;133(20):2233–2242.
  • Izak M, Bussel JB. Management of thrombocytopenia. F1000Prime Rep. 2014;6:45.
  • Santos FP, Tam CS, Kantarjian H, et al. Splenectomy in patients with myeloproliferative neoplasms: efficacy, complications and impact on survival and transformation. Leuk Lymphoma. 2014;55(1):121–127.
  • 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(6):761–770.
  • Ianotto JC, Boyer-Perrard F, Gyan E, et al. Efficacy and safety of pegylated-interferon alpha-2a in myelofibrosis: a study by the FIM and GEM French cooperative groups. Br J Haematol. 2013;162(6):783–791.
  • Talpaz M, Paquette R, Afrin L, et al. Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. J Hematol Oncol. 2013;6(1):81.
  • Vannucchi AM, Gisslinger H, Harrison CN, et al. EXPAND: a phase 1b, open-label, dose-finding study of ruxolitinib in patients with myelofibrosis (mf) and low platelet counts (50 × 109/l to 99 × 109/l) at baseline. Blood. 2015;126(23):2817–2817.
  • Vannucchi AM, Te Boekhorst PAW, Harrison CN, et al. EXPAND, a dose-finding study of ruxolitinib in patients with myelofibrosis and low platelet counts: 48-week follow-up analysis. Haematologica. 2019;104(5):947–954.
  • Talpaz M, Erickson-Viitanen S, Hou K, et al. Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. J Hematol Oncol. 2018;11(1):101.
  • Barosi G, Elliott M, Canepa L, et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies. Leuk Lymphoma. 2002;43(12):2301–2307.
  • Marchetti M, Barosi G, Balestri F, et al. Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial. J Clin Oncol. 2004;22(3):424–431.
  • Grunwald MR, Spivak JL. Ruxolitinib enhances platelet production in patients with thrombocytopenic myelofibrosis. J Clin Oncol. 2016;34(5):e38–40.
  • Rampal RK, Verstovsek S, Devlin SM, et al. Safety and efficacy of combined ruxolitinib and thalidomide in patients with myelofibrosis: initial results of a phase II study. Blood. 2018;132(Supplement 1):354–354.
  • Rampal RK, Verstovsek S, Devlin SM, et al. Safety and efficacy of combined ruxolitinib and thalidomide in patients with myelofibrosis: a phase II study. Blood. 2019;134(Supplement_1):4163–4163.
  • Rampal R, Verstovsek S, Devlin S, et al. Early results of a phase II study of combined ruxolitinib and thalidomide in patients with myelofibrosis: PS1467. HemaSphere. 2019;3:676–677.
  • Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. 2006;108(4):1158–1164.
  • Daver N, Cortes J, Newberry K, et al. Ruxolitinib in combination with lenalidomide as therapy for patients with myelofibrosis. Haematologica. 2015;100(8):1058–1063.
  • Begna KH, Pardanani A, Mesa R, et al. Long-term outcome of pomalidomide therapy in myelofibrosis. Am J Hematol. 2012;87(1):66–68.
  • 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.
  • Schlenk RF, Stegelmann F, Reiter A, et al. Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis. Leukemia. 2017;31(4):889–895.
  • Andrei M, Sindhu H, Wang JC. Two cases of myelofibrosis with severe thrombocytopenia and symptomatology successfully treated with combination of pomalidomide and ruxolitinib. Leuk Lymphoma. 2015;56(2):524–526.
  • Stegelmann F, Koschmieder S, Isfort S, et al. Ruxolitinib plus pomalidomide in myelofibrosis with anemia: results from the MPNSG-0212 combination trial (NCT01644110): S1608. Hemasphere. 2019;3:740–741.
  • Stegelmann F, Koschmieder S, Isfort S, et al. Updated results from the German Mpnsg-0212 combination trial: ruxolitinib plus pomalidomide in myelofibrosis with anemia. Blood. 2019;134(Suppl. 1):672.
  • Verstovsek S, Mesa RA, Foltz LM, et al. Phase 2 trial of PRM-151, an anti-fibrotic agent, in patients with myelofibrosis: stage 1 results: A713. Blood. 2014;124(21):713–713.
  • Verstovsek S, Hasserjian RP, Pozdnyakova O, et al. PRM-151 in myelofibrosis: efficacy and safety in an open label extension study. Blood. 2018;132(Supplement 1):686–686.
  • Verstovsek S, Talpaz M, Wadleigh M, et al. A randomized, double blind phase 2 study of 3 different doses of PRM-151 in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib: S828. Hemasphere. 2019;3:367.
  • 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.
  • Vannucchi AM, Mesa RA, Cervantes F, et al. Analysis of outcomes by patient subgroups in patients with myelofibrosis treated with pacritinib vs best available therapy (BAT) in the phase III Persist-1 Trial. Blood. 2015;126(23):58–58.
  • Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652–659.
  • Gerds AT, Savona MR, Scott BL, et al. Results of PAC203: a randomized phase 2 dose-finding study and determination of the recommended dose of pacritinib. Blood. 2019;134(Suppl. 1):667.
  • Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor-naive patients with myelofibrosis. J Clin Oncol. 2017;35(34):3844–3850.
  • Harrison CN, Vannucchi AM, Platzbecker U, et al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018;5(2):e73–e81.
  • Pardanani A, Harrison C, Cortes JE, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol. 2015;1(5):643–651.
  • Harrison CN, Schaap N, Vannucchi AM, et al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017;4(7):e317–e324.
  • Harrison CN, Schaap N, Vannucchi AM, et al. Fedratinib induces spleen responses and reduces symptom burden in patients with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF) and low platelet counts, who were either ruxolitinib-naïve or were previously treated with ruxolitinib. Blood. 2019;134(Supplement_1):4165–4165.
  • Ditschkowski M, Elmaagacli AH, Trenschel R, et al. Dynamic International Prognostic Scoring System scores, pre-transplant therapy and chronic graft-versus-host disease determine outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. Haematologica. 2012;97(10):1574–1581.
  • Kröger 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.
  • Passamonti F, Maffioli M. The role of JAK2 inhibitors in MPNs 7 years after approval. Blood. 2018;131(22):2426–2435.

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