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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 volume 29, pages 20–26 (2015)Cite this article

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Abstract

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

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Author notes

  1. G Barosi and A Tefferi: These two authors are both first authors of this work.

Authors and Affiliations

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

    G Barosi

  2. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    A Tefferi & A Pardanani

  3. Department of Haematology, Hospital del Mar-IMIM, Barcelona, Spain

    C Besses

  4. Department of Haematology, Uppsala University Hospital, Uppsala, Sweden

    G Birgegard

  5. Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

    F Cervantes

  6. Division of Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy

    G Finazzi & T Barbui

  7. Department of Hematology, Medical University of Vienna, Vienna, Austria

    H Gisslinger

  8. Academic Department of Hematology and Oncology, Johannes Wesling Teaching Hospital, Minden, Germany

    M Griesshammer

  9. Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

    C Harrison

  10. III Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

    R Hehlmann & A Reiter

  11. Inserm UMR 892, Institut de Recherche en Santé, Université de Nantes, Nantes, France

    S Hermouet

  12. Chair of MPN&MPNr-EuroNet, Institut de Recherche en Santé, Université de Nantes, Nantes, France

    S Hermouet

  13. Centre d'Investigations Cliniques-CIC 9504, Assistance Publique -Hôpitaux de Paris, Hôpital Saint-Louis,

    J-J Kiladjian

  14. Université Paris 7, Paris, France

    J-J Kiladjian

  15. Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    N Kröger

  16. Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA

    R Mesa

  17. Centre for Cancer Research and Cell Biology, Queen’s University, Belfast, UK

    M F Mc Mullin

  18. Division of Hematology, Ospedale di Circolo di Varese, Varese, Italy

    F Passamonti

  19. Department of Medicine Stockholm South Hospital, Karolinska Institute, Stockholm, Sweden

    J Samuelsson

  20. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    A M Vannucchi

  21. Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    R T Silver

  22. Department of Leukemia, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

    S Verstovsek

  23. Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy

    G Tognoni

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Correspondence to G Barosi.

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Competing interests

SH, CH, JJK, RM, AR, JS and MFMM received honoraria and had consulting role in Novartis; JJK, CH had a speakers’ bureau in Novartis; JJK, RH and CB received research funds from Novartis; G Birgegard had a consulting/advisory role in Shire; RM received research funding from Incyte, Gilead, Celgene, Genentech and NS Pharma; and SV received research funding from: Incyte Corporation, Astrazeneca, Lilly Oncology, Roche, Geron, NS Pharma, Bristol Myers Squibb, Novartis, Celgene, Infinity Pharmaceuticals, YM Biosciences, Seattle Genetics, Promedior, and Cell Therapeutics Inc. The remaining authors declare no conflict of interest.

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Barosi, G., Tefferi, A., Besses, C. 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 29, 20–26 (2015). https://doi.org/10.1038/leu.2014.250

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