Novel agents for the treatment of polycythemia vera: an insight into preclinical research and early phase clinical trials

ABSTRACT

Introduction

Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications.

Area covered

This article reviews the current data from completed early phase clinical trials in PV, either as monotherapy or in combination with the few currently approved agents.

Expert opinion

There remains an opportunity in PV management to improve efficacy and decrease risk of disease progression. Evolving data from use of long acting interferons are serving to clarifying the potential front line role of this therapy. JAK2 inhibition has made a significant impact on decreasing morbidity in patients with hydroxyurea resistant/refractory disease. New approaches may soon expand options including histone deactylase inhibitors (HDACi), either as monotherapy or combination therapy, which showed promising activity and symptomatic control of pruritus. Drugs targeting new molecular pathways (mammalian target of rapamycin, insulin receptor substrates 1/2, MDM2 protein) or the iron metabolism pathway are in early phase trial. Further translational studies assessing efficacy, long term complications, survival, and constitutional symptom control could pave a way for future success in PV drug development either as monotherapy or in combination.

KEYWORDS:

• Polycythemia Vera
• Myeloproliferative Neoplasm
• Erythrocytosis
• Hematologic Malignancy

Article highlights

• Current management of polycythemia vera (PV) is primarily focused on thrombosis risk reduction.

• Other considerations of PV therapy must consider constitutional symptom and bone marrow progression mitigation to acute leukemia or myelofibrosis.

• Active investigation into ideal front line therapy of interferon-based agents and their impact of decreasing janus kinase 2 allele burden will inform initial therapeutic decision making for patients and physicians.

• Combination therapy of current accessible and investigational agents may prove synergistic to improve and expand clinical outcomes.

• Early phase PV trials provide opportunities through new mechanisms of action to increase therapeutic options for second and third line.

This box summarizes key points contained in the article.

Declaration of interest

R Mesa is a Consultant for Novartis, Sierra Onc, La Jolla Pharma and has received research Support from Celgene, Incyte, Abbvie, Samus, Genetech,Promedior/CTI. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee received Consultancy fees from Incyte Corporation, Daiichi Sankyo, Trovagene, Ariad, Amgen, Pfizer, Cardinal Health, BMS/Celgene, Merck, Astellas, Premier, and Agios. He/she also receives research funding from Incyte Corporation, Amgen, Forma Therapeutics, Janssen, Genentech, and Novartis. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.