Definition and management of ruxolitinib treatment failure in myelofibrosis

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Ruxolitinib, a Janus kinase (JAK)-1 and JAK-2 inhibitor, is the first-in-class drug to be licensed in the United States for the treatment of high- and intermediate-risk myelofibrosis (MF). Several other JAK inhibitors are in development with some currently undergoing phase-3 clinical trial testing. None of the currently available JAK inhibitors are specific to mutant JAK2; their mechanism of action involves attenuation of JAK-STAT signaling with downregulation of proinflammatory cytokines, rather than selective suppression of the disease clone. Accordingly, while ruxolitinib and other JAK inhibitors are effective in controlling splenomegaly and alleviating constitutional symptoms, their benefit in terms of reversing bone marrow fibrosis or inducing complete or partial remissions appears to be limited. The experience to date with ruxolitinib shows that despite its salutary effects on quality of life, over half of the patients discontinue treatment within 2-3 years. In the current perspective, we examine the incidence and causes of ruxolitinib 'treatment failure' in MF patients based on our personal experience as well as a review of the published literature. We also discuss the challenges in defining and classifying ruxolitinib failure, and within the context of several clinical scenarios, we provide recommendations for the post-ruxolitinib management of MF patients.

Original languageEnglish (US)
Pages (from-to)e268
JournalBlood Cancer Journal
Volume4
Issue number12
DOIs
StatePublished - Jan 1 2014

Fingerprint

Primary Myelofibrosis
Treatment Failure
Janus Kinases
Janus Kinase 1
Janus Kinase 2
Phase III Clinical Trials
Splenomegaly
INCB018424
Down-Regulation
Clone Cells
Quality of Life
Cytokines
Incidence
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Definition and management of ruxolitinib treatment failure in myelofibrosis. / Pardanani, Animesh D; Tefferi, Ayalew.

In: Blood Cancer Journal, Vol. 4, No. 12, 01.01.2014, p. e268.

Research output: Contribution to journalArticle

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