Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

How can we know if new drugs are effective in myeloproliferative neoplasm-associated myelofibrosis?

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout


  1. Barosi G, Tefferi A, Besses C, Birgegard G, Cervantes F, Finazzi G et al. Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). Leukemia 2015; 29: 20–26.

    Article  CAS  Google Scholar 

  2. Barosi G . Setting appropriate goals for the next generation of clinical trials in myelofibrosis. Curr Hematol Malig Rep 2015; 10: 362–369.

    Article  Google Scholar 

  3. Barosi G, Tefferi A, Barbui T . Do current response criteria in classical Ph-negative myeloproliferative neoplasms capture benefit for patients? Leukemia 2012; 26: 1148–1149.

    Article  CAS  Google Scholar 

  4. 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 

  5. 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 

  6. Mascarenhas J, Heaney ML, Najfeld V, Hexner E, Abdel-Wahab O, Rampal R et al. Proposed criteria for response assessment in patients treated in clinical trials for myeloproliferative neoplasms in blast phase (MPN-BP): formal recommendations from the post-myeloproliferative neoplasm acute myeloid leukemia consortium. Leuk Res 2012; 36: 1500–1504.

    Article  Google Scholar 

  7. Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in acute myeloid leukemia. J Clin Oncol 2003; 21: 4642–4649.

    Article  Google Scholar 

  8. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013; 122: 872–884.

    Article  CAS  Google Scholar 

  9. Appelbaum FR, Rosenblum D, Arceci RJ, Carroll WL, Breitfeld PP, Forman SJ et al. End points to establish the efficacy of new agents in the treatment of acute leukemia. Blood 2007; 109: 1810–1816.

    Article  CAS  Google Scholar 

  10. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–4997.

    CAS  Google Scholar 

  11. Cheson BD . Staging and response assessment in lymphomas: the new Lugano classification. Chin Clin Oncol 2015; 4: 5.

    PubMed  Google Scholar 

  12. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.

    Article  CAS  Google Scholar 

  13. Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 2011; 117: 4691–4695.

    Article  CAS  Google Scholar 

  14. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. 1. Blood 2006; 108: 419–425.

    Article  CAS  Google Scholar 

  15. Lübbert M, Suciu S, Hagemeijer A, Rüter B, Platzbecker U, Giagounidis A et al. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group. Ann Hematol 2015; 95: 191–199.

    Article  Google Scholar 

  16. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009; 10: 223–232.

    Article  CAS  Google Scholar 

  17. Verstovsek S, Mesa RA, Gotlib J et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366: 799–807.

    Article  CAS  Google Scholar 

  18. 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: 787–798.

    Article  CAS  Google Scholar 

  19. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation, and Research (CDER) Center for Biologics Evaluation and Research (CBER) (2007). Guidance for industry clinical trial endpoints for the approval of cancer drugs and biologics.

  20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228–247.

    Article  CAS  Google Scholar 

  21. US Food and Drug Administration. Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Federal Register 2009; 74: 65132–133.

  22. European Medicines Agency Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. Available at: (accessed 23 April 2015).

  23. Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol 2015; 1: 643–651.

    Article  Google Scholar 

  24. Komrokji RS, Seymour JF, Roberts AW, Wadleigh M, To LB, Scherber R et al. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Blood 2015; 125: 2649–2655.

    Article  CAS  Google Scholar 

  25. Mead AJ, Milojkovic D, Knapper S, Garg M, Chacko J, Farquharson M et al. Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis:results of the UK ROBUST trial. Br J Haematol 2015; 170: 29–39.

    Article  CAS  Google Scholar 

  26. Deininger M, Radich J, Burn TC, Huber R, Paranagama D, Verstovsek S . The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis. Blood 2015; 126: 1551–1554.

    Article  CAS  Google Scholar 

  27. Angona A, Alvarez-Larrán A, Bellosillo B, Longarón R, Fernández-Rodríguez C, Besses C . Dynamics of JAK2 V617F allele burden of CD34(+) haematopoietic progenitor cells in patients treated with ruxolitinib. Br J Haematol 2015; 172: 639–642.

    Article  Google Scholar 

  28. Breccia M, Molica M, Colafigli G, Alimena G . Improvement of bone marrow fibrosis with ruxolitinib: will this finding change our perception of the drug? Expert Rev Hematol 2015; 8: 387–389.

    Article  CAS  Google Scholar 

  29. Kremyanskaya M, Mascarenhas J, Rampal R, Hoffman R . Development of extramedullary sites of leukaemia during ruxolitinib therapy for myelofibrosis. Br J Haematol 2014; 167: 144–146.

    Article  CAS  Google Scholar 

  30. Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA et al. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica 2015; 100: 1139–1145.

    Article  CAS  Google Scholar 

  31. Revicki DA, Osoba D, Fairclough D, Barofsky I, Berzon R, Leidy NK et al. Recommendations on health-related quality of life research to support labeling and promotional claims in the United States. Qual Life Res 2000; 9: 887–900.

    Article  CAS  Google Scholar 

  32. Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010; 363: 1117–1127.

    Article  CAS  Google Scholar 

  33. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF et al. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica 2015; 100: 479–488.

    Article  CAS  Google Scholar 

  34. Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V et al. 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: 4047–4053.

    Article  CAS  Google Scholar 

  35. Abdelrahman RA, Begna KH, Al-Kali A, Hogan WJ, Litzow MR, Tefferi A . Revised assessment of response and long-term discontinuation rates among 111 patients with myelofibrosis treated with momelotinib or ruxolitinib. Leukemia 2015; 29: 498–500.

    Article  CAS  Google Scholar 

  36. Fonseca E, Silver RT, Kazis LE, Iqbal SU, Rose M, Khan N . Ruxolitinib discontinuation in patients with myelofibrosis: an analysis from clinical practice. Blood 2013; 122: Abstract N.2833.

    Google Scholar 

  37. Le Tourneau C, Lee JJ, Siu LL . Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst 2009; 101: 708–720.

    Article  CAS  Google Scholar 

  38. Palmer J, Chai X, Martin PJ, Weisdorf D, Inamoto Y, Pidala J et al. Failure-free survival in a prospective cohort of patients with chronic graft-versus-host disease. Haematologica 2015; 100: 690–695.

    Article  Google Scholar 

  39. Pardanani A, Tefferi A . Definition and management of ruxolitinib treatment failure in myelofibrosis. Blood Cancer J 2014; 4: e268.

    Article  CAS  Google Scholar 

Download references


Profs Eli Estey (University of Washington) and Charles Bennett (Medical College S. Carolina) kindly reviewed the typescript. GB acknowledges support 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 RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme.

Author information

Authors and Affiliations


Corresponding author

Correspondence to G Barosi.

Ethics declarations

Competing interests

GB participated in advisory boards of Novartis and Sanofi.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barosi, G., Gale, R. How can we know if new drugs are effective in myeloproliferative neoplasm-associated myelofibrosis?. Leukemia 30, 1453–1455 (2016).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links