Momelotinib in myelofibrosis

ABSTRACT

Introduction

Myelofibrosis (MF) is a hematologic disease characterized by bone marrow fibrosis, cytopenias, splenomegaly, and constitutional symptoms. Recent years have seen the emergence of novel therapeutic agents, notably ruxolitinib and fedratinib, which target the Janus kinases (JAK) pathway. However, their myelosuppressive effect coupled with the persistence, and even worsening anemia remains a significant challenge, leading usually to treatment discontinuation.

Areas covered

This review focuses on Momelotinib (MMB), a unique JAK inhibitor that has shown promise in MF treatment, particularly in improving anemia. MMB inhibits type 1 kinase activin A receptor or activin receptor-like kinase-2 (ACVR1/ALK2), with consequent rebalancing of the SMAD pathways and reduced transcription of hepcidin. Moreover, it seems that MMB could reduce the serum levels of several inflammatory cytokines responsible for anemia. Clinical trials have demonstrated MMB’s efficacy in reducing spleen size, alleviating symptoms, and improving anemia, with a favorable safety profile compared to other JAK inhibitors, both in treatment-naïve and in pre-treated patients.

Expert opinion

Due to its mechanism of action, MMB represents a valuable therapeutic option in MF, addressing the clinical challenge of anemia and potentially improving outcomes for patients with hematologic malignancies. Ongoing research explores MMB’s potential in acute myeloid leukemia and combination therapies.

KEYWORDS:

• Momelotinib
• myelofibrosis
• therapy
• JAK inhibitor

Article highlights

• Anemia negatively affects the outcomes of patients with MF.

• JAK inhibitors such as ruxolitinib or fedratinib could worsen anemia.

• Momelotinib acts by inhibiting JAK2 and ACVR1.

• Several studies proved the efficacy of MMB with low toxicity on red blood cells.

• Momelotinib represents a good treatment option for anemic MF patients.

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.

Additional information

Funding

The present study is supported in part by Progetto Ricerca Finalizzata PNRR-MAD-2022-12375673 (Next Generation EU, M6/C2_CALL 2022), Italian Ministry of Health, Rome, Italy.