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Ruxolitinib and survival improvement in patients with myelofibrosis

Leukemia volume 29, pages 739–740 (2015)Cite this article

Subjects

We read with interest the paper by Barosi et al.1 discussing the survival improvement with ruxolitinib in patients with primary myelofibrosis (PMF). Although we agree with some of their points, we would like to address a few of their conclusions.

Regarding potential selection bias, we agree that not every myelofibrosis (MF) patient with splenomegaly and IPSS intermediate-2/high-risk disease entered the COMFORT-2 trial. However, this is an issue in most cancer clinical trials. Although there were patients in COMFORT-2 who were lost to follow-up, a patient survival update, coauthored by Dr Barosi himself, documented an enhanced survival benefit with ruxolitinib.2 The primary end point of the COMFORT trial was reduction in spleen size.3, 4 Whether treatment with ruxolitinib affects survival in treated patients could not be completely answered by these studies because of the crossover design (patient on control arms were allowed to ‘crossover’ and receive ruxolitinib). For example, in the IRIS trial (chronic myelogenous leukemia—CML), the imatinib arm never demonstrated a survival benefit compared with the standard treatment arm (due to crossover), despite the well-known outstanding anti-CML activity of imatinib.5 It is true that such a question could be addressed by conducting an experimental randomized trial comparing survival in treated versus untreated patients; however, this is not considered ethical now given the documented improvements in symptoms and quality of life elicited by ruxolitinib,3, 4 and it was not considered feasible at the time the COMFORT trials were designed.

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References

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, University Hospital Ospedale di Circolo e Fondazione Macchi, Varese, Italy

    F Passamonti

  2. Department of Critical Care, Section of Hematology, University of Florence, Florence, Italy

    A M Vannucchi

  3. Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

    F Cervantes

  4. Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, UK

    C Harrison

  5. Division of Hematology, Ospedale Niguarda Cà Granda, Milano, Italy

    E Morra

  6. Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA

    H Kantarjian & S Verstovsek

Authors
  1. F Passamonti
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  2. A M Vannucchi
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  3. F Cervantes
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  4. C Harrison
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  5. E Morra
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  6. H Kantarjian
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  7. S Verstovsek
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Corresponding author

Correspondence to F Passamonti.

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Competing interests

FP participated to advisory boards of Novartis, Sanofi, Celgene, Roche. AMV received speaker honoraria and advisory board participation from Novartis; AMV institution received research support from Novartis. FC participated to Advisory Boards for Novartis, Sanofi-Aventis and Gilead and Speaker bureau of Novartis and CTI; CH participated to advisory board or received lecture honoraria from Novartis, CTI, YM Bioscience, CTI, Sanofi, Celgene, Gilead and Shire, Institutional research support from Shire and Novartis; EM and HK have no conflict of interest to declare. SV received Research support from Incyte for conducting the clinical studies.

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Passamonti, F., Vannucchi, A., Cervantes, F. et al. Ruxolitinib and survival improvement in patients with myelofibrosis. Leukemia 29, 739–740 (2015). https://doi.org/10.1038/leu.2014.282

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