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JAK2V617F allele burden ⩾50% is associated with response to ruxolitinib in persons with MPN-associated myelofibrosis and splenomegaly requiring therapy

Leukemia volume 30, pages 1772–1775 (2016)Cite this article

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Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is approved for the treatment of myeloproliferative neoplasm (MPN)-associated myelofibrosis based on the results of COMFORT-I and -II trials showing that therapy reduced splenomegaly, reversed myelofibrosis-associated symptoms and improved quality of life.1, 2 In 2006, the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) categorized response in myelofibrosis into complete or partial response or clinical improvement.3 However, these response criteria were not used in the COMFORT trials where the IWG-MRT definition of spleen response was replaced by a 35% reduction in nuclear magnetic resonance- or computed tomography-measured spleen volume. Discordance between IWG-MRT response criteria and those used in the COMFORT studies is problematic when physicians try to determine which persons with MPN-associated myelofibrosis and splenomegaly might benefit from ruxolitinib therapy.

We evaluated spleen response using 2013 IWG-MRT criteria in 69 consecutive subjects with MPN-associated myelofibrosis receiving ruxolitinib for splenomegaly interrogating variables associated with spleen response.

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References

  1. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366: 799–807.

    Article  CAS  Google Scholar 

  2. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012; 366: 787–798.

    Article  CAS  Google Scholar 

  3. Tefferi A, Barosi G, Mesa RA, Cervantes F, Deeg HJ, Reilly JT et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood 2006; 108: 1497–1503.

    Article  CAS  Google Scholar 

  4. Barosi G, Vannucchi AM, De Stefano V, Pane F, Passamonti F, Rambaldi A et al. Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper. Leuk Res 2014; 38: 155–160.

    Article  Google Scholar 

  5. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A 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: 1703–1708.

    Article  CAS  Google Scholar 

  6. Barosi G, Viarengo G, Pecci A, Rosti V, Piaggio G, Marchetti M et al. Diagnostic and clinical relevance of the number of circulating CD34(+) cells in myelofibrosis with myeloid metaplasia. Blood 2001; 98: 3249–3255.

    Article  CAS  Google Scholar 

  7. Patel KP, Newberry KJ, Luthra R, Jabbour E, Pierce S, Cortes J et al. Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib. Blood 2015; 126: 790–797.

    Article  CAS  Google Scholar 

  8. Guglielmelli P, Rotunno G, Bogani C, Mannarelli C, Giunti L, Provenzano A et al. Ruxolitinib is an effective treatment for CALR-positive patients with myelofibrosis. Br J Haematol 2015; e-pub ahead of print 25 August 2015 doi:10.1111/bjh.13644.

    Article  Google Scholar 

  9. Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM 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: 1395–1398.

    Article  CAS  Google Scholar 

  10. Rampal R, Al-Shahrour F, Abdel-Wahab O, Patel JP, Brunel JP, Mermel CH et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood 2014; 123: e123–e133.

    Article  Google Scholar 

  11. Plo I, Nakatake M, Malivert L, de Villartay JP, Giraudier S, Villeval JL et al. JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders. Blood 2008; 112: 1402–1412.

    Article  CAS  Google Scholar 

  12. Medinger M, Skoda R, Gratwohl A, Theocharides A, Buser A, Heim D et al. Angiogenesis and vascular endothelial growth factor-/receptor expression in myeloproliferative neoplasms: correlation with clinical parameters and JAK2-V617F mutational status. Br J Haematol 2009; 146: 150–157.

    Article  CAS  Google Scholar 

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Acknowledgements

Supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) ‘Special Program Molecular Clinical Oncology 5 × 1000’ to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative). A detailed description of the AGIMM project is available at http://www.progettoagimm.it. RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme.

Author contributions

Giovanni Barosi designed the study, analyzed the results and prepared the typescript. Valentina Poletto contributed to the JAK2V617F mutation detection by allele-specific PCR. Margherita Massa helped to design the study. Rita Campanelli, Elisa Bonetti, Adriana Carolei, Stefana Impera, Maurizio Musso and Alessandra Crescimanno collected clinical data. Laura Villani analyzed JAK2V617F, CALR and MPL mutations. Gianluca Viarengo assayed CD34-positive cells. Paolo Catarsi helped with the JAK2V617F assay with quantitative PCR. Catherine Klersy helped with the survival and competing risk analysis. Vittorio Rosti and Robert Peter Gale helped design the study and write the manuscript.

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Authors and Affiliations

  1. Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy

    G Barosi, L Villani, E Bonetti, P Catarsi, V Poletto, R Campanelli, A Carolei, M Massa & V Rosti

  2. Biometry and Clinical Epidemiology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy

    C Klersy

  3. Hematology, Presidio Ospedaliero Garibaldi-Nesima, Catania, Italy

    S Impera

  4. Department of Cellular Biotechnology and Hematology, University of Rome, La Sapienza, Italy

    R Latagliata

  5. Immunohematology and Transfusion Service, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy

    G Viarengo

  6. Dipartimento Oncologico ‘La Maddalena’, UO di Oncologia e Trapianto di Midollo, Palermo, Italy

    M Musso & A Crescimanno

  7. Division of Experimental Medicine, Department of Medicine, Haematology Research Centre, Imperial College London, London, UK

    R P Gale

Authors
  1. G Barosi
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  3. L Villani
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  7. R Campanelli
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  8. S Impera
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  9. R Latagliata
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  11. A Carolei
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  12. M Massa
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  13. M Musso
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  14. A Crescimanno
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  15. R P Gale
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  16. V Rosti
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Corresponding author

Correspondence to G Barosi.

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Competing interests

GB participated in advisory boards from Novartis and Sanofi. RPG is a part-time employee of Celgene Corp. The other authors declare no conflict of interest.

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Barosi, G., Klersy, C., Villani, L. et al. JAK2V617F allele burden ⩾50% is associated with response to ruxolitinib in persons with MPN-associated myelofibrosis and splenomegaly requiring therapy. Leukemia 30, 1772–1775 (2016). https://doi.org/10.1038/leu.2016.45

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