Ruxolitinib for the treatment of patients with polycythemia vera

Abstract

Polycythemia vera (PV) is a hematopoietic proliferative disorder associated with Janus-associated kinase/signal transducer and activator of transcription pathway dysregulation resulting in erythrocytosis and, possibly, leukocytosis and thrombocytosis. Patients diagnosed with PV experience a broad range of symptoms associated with a reduced quality of life, often develop splenomegaly, and have an increased risk of death compared with age-matched subjects without PV. Current treatment options, notably hydroxyurea, help with disease management; however, insufficient efficacy or progressive resistance occurs in some patients, highlighting the need for new treatment options. Ruxolitinib is an oral JAK1/JAK2 inhibitor that has been evaluated in Phase II and III clinical trials in patients with PV, who are intolerant of or resistant to hydroxyurea. In this setting, ruxolitinib treatment has demonstrated normalization of blood cell counts, reduction in splenomegaly and improvements in PV-related symptom burden.

Keywords:

• erythrocytosis
• Janus kinase 1
• Janus kinase 2
• myeloproliferative neoplasm
• polycythemia vera
• ruxolitinib
• splenomegaly
• thrombocytosis

Financial & competing interests disclosure

J-J Kiladjian has received honoraria and research funding from Novartis Pharmaceuticals and has served on advisory boards for Novartis Pharmaceuticals. E Winton has received research funding from Gilead Sciences Inc., Incyte Corporation, Pfizer, and Sanofi, and has served on advisory boards for Incyte Corporation. M Talpaz has received research funding from ARIAD, Bristol-Myers Squibb, Sanofi, Incyte Corporation, and Pfizer. S Verstovsek has received research funding from AstraZeneca, Bristol Myers Squibb, Celgene, Cell Therapeutics Inc., Galena BioPharma, Geron, Gilead Sciences Inc., Incyte Corporation, Infinity Pharmaceuticals, Lilly Oncology, NS Pharma, Pfizer, Promedior, Roche, and Seattle Genetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript and performed by C Pfeiffenberger (Complete Healthcare Communications, Inc.), whose work was funded by Incyte Corporation.

Key issues

• Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with erythrocytosis, leukocytosis, and thrombocytosis.

• PV is nearly always associated with Janus-associated kinase/signal transducer and activator of transcription pathway-activating mutations.

• Mortality is increased in patients with PV, primarily because of increased incidence of thrombotic events and disease transformation to myelofibrosis or acute myeloid leukemia.

• Patients with PV experience a broad-ranging symptom burden that negatively affects their quality of life.

• High-risk patients with PV who become intolerant of or resistant to hydroxyurea have limited treatment options.

• Ruxolitinib is an oral JAK1/JAK2 inhibitor with rapid absorption and good bioavailability. Collectively, Phase II and III safety and efficacy results support ruxolitinib as the first US FDA-approved treatment option for patients with PV for whom hydroxyurea has failed.

• In the PV setting, ruxolitinib controls hematocrit, reduces the need for phlebotomy, normalizes blood cell counts, reduces splenomegaly, and improves PV-related symptom severity.

• Ruxolitinib has a favorable tolerability profile; most adverse events were grade 1 or 2 and managed by dose interruptions and/or reductions.