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Does ruxolitinib improve survival of persons with MPN-associated myelofibrosis? Should it?

Leukemia volume 28, pages 2267–2270 (2014)Cite this article

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JAK2-activating mutations are linked to development of myeloproliferative neoplasms (MPNs), a discovery that revolutionized the therapy of persons with MPN-associated myelofibrosis. Targeting the JAK/STAT pathway with ruxolitinib, a JAK1/JAK2 inhibitor, suppresses heamatopoiesis and pro-inflammatory cytokines, reduces splenomegaly and disease-related symptoms.1, 2, 3, 4 These effects are not specific for the neoplastic clone and the response rates are similar in persons with and without the JAK2V617F and other JAK2 mutations.5 Based on these data, ruxolitinib was approved by the US Food and Drug Administration (FDA) for therapy of splenomegaly in persons with >intermediate-risk MPN-associated myelofibrosis (staging system unspecified), and by the European Medicines Agency (EMA) for therapy of splenomegaly and/or symptoms in persons with MPN-associated myelofibrosis for all disease stages.

Despite clear clinical benefit, a key question is whether ruxolitinib therapy improves survival of persons with MPN-associated myelofibrosis. Recently there have been several reports of better survival in persons with MPN-associated myelofibrosis receiving ruxolitinib compared with placebo or the best available therapy. This claim is based on analyses of data from the COMFORT-I and COMFORT-II randomized trials6,7 and two case–control studies.8,9

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Acknowledgements

GB was 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).

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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 Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA

    M-J Zhang

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

    R Peter Gale

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  1. G Barosi
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Correspondence to G Barosi.

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Competing interests

RPG is a part-time employee of Celgene Corp. GB participated in advisory boards from Novartis and Sanofi. M-JZ declares no conflict of interest.

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Barosi, G., Zhang, MJ. & Gale, R. Does ruxolitinib improve survival of persons with MPN-associated myelofibrosis? Should it?. Leukemia 28, 2267–2270 (2014). https://doi.org/10.1038/leu.2014.220

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