Light and shade of ruxolitinib: positive role of early treatment with ruxolitinib and ruxolitinib withdrawal syndrome in patients with myelofibrosis

ABSTRACT

Introduction

Myelofibrosis (MF) is characterized by ineffective and hepatosplenic extramedullary hematopoiesis due to fibrotic changes in the bone marrow and systemic manifestations due to aberrant cytokine release. Ruxolitinib (RUX) is the first JAK1/JAK2 inhibitor that is clinically approved to treat splenomegaly by ameliorating inflammatory cytokines and myeloproliferation in MF.

Areas covered

Patients with less advanced MF may also achieve better outcome and successful treatment with RUX. However, approximately 40% of the patients failed to achieve a stable response or have shown to be intolerant to RUX, and most of them discontinued RUX. In patients who need to discontinue or reduce the dose of RUX for any reason, RUX is known to induce a paradoxical accumulation of JAK activation loop phosphorylation that is causing RUX discontinuation syndrome (RDS). To review the topic of MF and RUX, we searched relevant literatures using PubMed.

Expert opinion

RUX treatment in lower IPSS risk patients who present with splenomegaly and disease-associated symptoms can be helpful. A careful discontinuation strategy with steroids may reduce the probability of RDS, and the recognition of RDS with early re-introduction of RUX is important in the treatment of severe cases of RDS.

KEYWORDS:

• Myelofibrosis
• ruxolitinib
• early treatment
• adverse events
• ruxolitinib discontinuation syndrome

Article highlights

• Ruxolitinib treatment in lower IPSS risk patients who present with splenomegaly and disease-associated symptoms can be helpful.

• Anemia and thrombocytopenia were frequently reported as ruxolitinib-associated adverse event. Adequate control of adverse events with dose modification and transfusion is necessary.

• Over 30% of the patients have discontinued ruxolitinib therapy, and some of them experienced prompt onset of withdrawal symptoms.

• A careful discontinuation strategy with steroids may reduce the probability of ruxolitinib discontinuation syndrome, and physicians should always consider the re-introduction of ruxolitinib in a severe ruxolitinib discontinuation syndrome case.

Declaration of Interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Additional information

Funding

This paper was not funded.