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Review Polycythaemia Vera
Optimising the Use of Ruxolitinib in
Inadequately Controlled Polycythaemia Vera
Jean-Jacques Kiladjian, 1 Yvonne Francis 2 and Juliette Soret 1
1. APHP, Hopital Saint-Louis, Centre d’Investigation Clinique, INSERM CIC 1427, Paris, France; 2. Haematology Clinical Nurse Specialist,
Guy’s Hospital, London, UK
P olycythaemia vera (PV) is an uncommon chronic myeloproliferative neoplasm characterised by increased red-cell mass. The
condition is currently managed by phlebotomy and/or palliative cytoreductive therapy, most commonly using hydroxyurea (HU).
However, around 25% of patients have an inadequate response and/or unacceptable adverse effects; furthermore, patients with
resistance to HU appear to have shorter survival than other patients with PV. Recently, a second-line treatment has become available.
Ruxolitinib, an oral inhibitor of the Janus kinase (JAK) 1 and JAK 2 tyrosine kinases, has recently received regulatory approval for the
treatment of patients with PV who are resistant to or intolerant of HU. This treatment offers the potential to significantly reduce phlebotomy
requirements and improve the symptom burden. However, in order to determine which patients will benefit most from ruxolitinib, it is
necessary to identify those who are inadequate responders to HU, a definition that is not currently consensual in the literature. Five
patient groups, for whom ruxolitinib may be a beneficial second-line treatment option, have been proposed. These comprise patients who
are at high risk and retain a high symptom burden after HU, require frequent phlebotomy, have an elevated leukocyte count, are intolerant
to HU or interferon, or have palpable splenomegaly.
Keywords Myeloproliferative neoplasm, polycythaemia
Disclosure: Jean-Jaques Kiladjian has received
institutional research funding from Novartis and AOP
Orphan and particpated on advisory boards for Novartis,
Shire and AOP Orphan. Yvonne Francis and Juliette Soret
have nothing to disclose in relation to this article. This
study involves a review of the literature and did not
involve any studies with human or animal subjects
performed by any of the authors.
Acknowledgements: Medical writing support was
provided by Katrina Mountfort, for Touch Medical Media,
UK, supported by Novartis.
Authorship: All named authors meet the International
Committee of Medical Journal Editors (ICMJE) criteria
for authorship of this manuscript, take responsibility
for the integrity of the work as a whole, and have
given final approval to the version to be published.
Open Access: This article is published under the
Creative Commons Attribution Noncommercial License,
which permits any non-commercial use, distribution,
adaptation and reproduction provided the original
author(s) and source are given appropriate credit.
Received: 13 September 2016
Accepted: 11 October 2016
Citation: European Oncology & Haematology,
2016;12(2):81–6 Corresponding Author: Jean-Jaques Kiladjian, APHP,
Hopital Saint-Louis, Centre d’Investigation Clinique,
INSERM CIC 142, 1 avenue Claude Vellefaux, 75475 Paris
Cedex 10, France. E: firstname.lastname@example.org
Support: The publication of this article was supported
by Novartis. The views and opinions expressed are
those of the authors and do not necessarily reflect
those of Novartis. The authors provided Novartis
with the opportunity to review the article for
scientific accuracy before submission. Any resulting
changes were made at the author’s discretion.
Polycythaemia vera (PV) is a chronic myeloproliferative neoplasm characterised by unregulated
proliferation of red blood cells, and sometimes leukocytes and platelets in the absence of a
recognisable physiological stimulus. 1–4 Increased red blood cell mass leads to hyperviscosity of the
blood and increased risk of thrombosis. In addition, patients may have a high symptom burden that
includes intractable pruritus, fatigue and altered quality of life (QoL). 5,6 If inadequately controlled,
the condition can lead to serious complications including increased risk of cardiovascular
events, together with the development of splenomegaly as the disease progresses. 1 The disease
progresses slowly and is associated with a reduced life expectancy; 3 the median survival of PV
patients is 14.1 years, 7 and is lower in patients who are resistant or intolerant to hydroxyurea
(HU), as well as patients at high risk of thrombosis. In addition, PV may transform into acute
myelogenous leukaemia (AML) in up to 15% of patients every 10 years 7,9 or myelofibrosis (MF) in
up to 10% of patients every 10 years. 10–12
PV is an uncommon but not so rare condition: its annual incidence is approximately
2.8 per 100,000 population of men and approximately 1.3 per 100,000 population of women.
The prevalence of PV is approximately 22 cases per 100,000 people. 3 The median age
at presentation is in the sixth decade but one third of patients with PV are under 50 years
of age. 13
Despite advances in the treatment of PV, the symptom burden is often underestimated by
physicians and is poorly managed, resulting in impaired QoL, 14 restricted participation in social
events and physical activity. 6 Most therapies in PV appropriately aim to reduce thrombotic risk,
which is the first cause of mortality and morbidity in the short term, but do not address PV
symptoms. Recently, the Janus kinase (JAK) inhibitor ruxolitinib was approved for patients with
PV who are intolerant to or resistant of HU, the most widely used first-line therapy for high-risk
patients with PV. However, ruxolitinib is not commonly used in clinical practice 15 and there is
a need to identify patients who will derive the most benefit from this therapy and to define
inadequately controlled PV. This article aims to examine what constitutes inadequate control in
PV and explores current treatment strategies.
Current strategies for the management of polycythaemia vera
The primary aim of present PV therapy is not to eliminate disease, but to reduce the incidence
of thrombotic events while minimising the risk of haematological transformation to AML or MF. 16
Patients with PV are therefore treated according to their risk for thrombosis: patients aged <60
years and with no history of thrombosis are considered low risk while those age >60 years and/
or with history of thrombosis are high risk (see Table 1). 17–19 Some centres will also treat according
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