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Reply to Passamonti et al: ruxolitinib and survival improvement in patients with myelofibrosis

Leukemia volume 29, page 740 (2015)Cite this article

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Passamonti et al. and we agree it is difficult to know whether ruxolitinib improves survival of persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. This issue has broad implications because it focuses on the ethics of medical research: conclusions about what is true should be deduced from strong scientific evidence, especially when a conclusion alters how people will be treated. If ruxolitinib improves survival of persons with MPN-associated myelofibrosis, we need to change our therapy paradigm from problem or symptom oriented to disease oriented. If subjects in the COMFORT-I and -II trials receiving ruxolitinib really have better survival than controls, the logical conclusion is that everyone with intermediate-II or high-risk disease and splenomegaly ⩾5 cm sh ould receive ruxolitinib regardless of signs, symptoms, prior therapy, preferences, risks, costs and so on, because prolongation of life is sacrosanct.

Passamonti et al. also agree the strength of evidence favoring a survival benefit with ruxolitinib is not overwhelming because of the complexities of clinical trials design. If the purpose of a study is determine whether survival is improved, survival or a validated surrogate, must be a primary or co-primary end point. Statistical engineering to deduce a survival impact when this requirement is not met is prone to biases, which can nullify or modify the conclusion.

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References

  1. Barosi G, Tefferi A, Besses C, Birgegard G, Cervantes F, Finazzi G et al. Clinical endpoints for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). Leukemia, e-pub ahead of print 25 August 2014; doi:10.1038/leu.2014.250.

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Authors and Affiliations

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

    G Barosi

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

    R P Gale

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  1. G Barosi
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  2. R P Gale
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Correspondence to R P Gale.

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Barosi, G., Gale, R. Reply to Passamonti et al: ruxolitinib and survival improvement in patients with myelofibrosis. Leukemia 29, 740 (2015). https://doi.org/10.1038/leu.2014.312

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