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Ruxolitinib

In the Treatment of Myelofibrosis

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Abstract

Ruxolitinib is a selective inhibitor of Janus kinases (JAK) 1 and 2, which are involved in the signalling pathway of various cytokines and growth factors essential to haematopoiesis. JAK 1 and 2 are implicated in the development of myelofibrosis, as well as other haematological malignancies. Ruxolitinib is the first agent approved for the treatment of myelofibrosis.

In a randomized, double-blind, placebo-controlled, multicentre trial (COMFORT-I) in patients with myelofibrosis, significantly more ruxolitinib than placebo recipients achieved a ≥35% reduction in spleen volume (primary endpoint) at 24 weeks. In a randomized, open-label, multicentre trial (COMFORT-II) in patients with myelofibrosis, significantly more ruxolitinib than best available therapy recipients achieved the same primary endpoint at 48 weeks.

Significantly more ruxolitinib than placebo recipients achieved a ≥50% reduction in Total Symptom Score at 24 weeks in COMFORT-I. Ruxolitinib generally improved health-related quality-of-life scores, while best available therapy was generally associated with worsened scores at 48 weeks in COMFORT-II. In COMFORT-I, overall survival data appeared to favour ruxolitinib over placebo; of note, most placebo recipients had crossed over to receive ruxolitinib. In COMFORT-II, a significant difference in overall survival between ruxolitinib and best available therapy was not shown; this trial was not powered to detect such a difference.

In clinical trials in patients with myelofibrosis, ruxolitinib was generally associated with an acceptable tolerability profile. In the placebo-controlled trial, the most commonly reported grade 3 or 4 adverse events in ruxolitinib recipients were thrombocytopenia, anaemia and neutropenia. These haematological adverse events were mainly managed with dosage interruptions/reductions and/or transfusions, and rarely resulted in discontinuation.

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Acknowledgements and Disclosures

The manuscript was reviewed by: G. Barosi, Laboratory of Clinical Epidemiology and Center for the Study of Myelofibrosis, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; R.A. Mesa, Division of Hematology & Medical Oncology, Mayo Clinic, Scottsdale, AZ, USA; F. Ravandi, Department of Leukemia, University of Texas – MD Anderson Cancer Center, Houston, TX, USA; S. Verstovsek, Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Lily P. H. Yang & Gillian M. Keating

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  1. Lily P. H. Yang
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Correspondence to Lily P. H. Yang.

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Yang, L.P.H., Keating, G.M. Ruxolitinib. Drugs 72, 2117–2127 (2012). https://doi.org/10.2165/11209340-000000000-00000

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