Developing strategies to reduce the duration of therapy for patients with myeloproliferative neoplasms

ABSTRACT

Introduction

All current treatment strategies for myeloproliferative neoplasms (MPN) patients with the exception of allogeneic stem cell transplant (ASCT) are continuously administered. Treatment approaches that reduce the degree of minimal residual disease (MRD) might permit possible drug holidays or potential cures.

Area covered

Authors discuss the presently available agents and those that are under clinical development that might induce a state of MRD and can be administered intermittently. Data extracted from a comprehensive search of peer review literature performed in Pubmed as well as information presented in scientific meetings.

Expert opinion

Currently, the only potential curative treatment for MPN is ASCT. ASCT requires a period of intense treatment but ultimately allows the patient to enjoy a period independent of continued treatment. There is evidence that intermittent use of busulfan or prolonged use of IFN-α can induce hematological remissions that are sustained for prolonged periods of time, allowing for drug holidays. The experimental drug Imetelstat is a promising drug that has been reported to prolong survival in very high-risk myelofibrosis patients after a limited period of time of administration. New experimental drugs and drug combinations that target the malignant clone and/or microenvironmental abnormalities have the potential to eliminate MRD, which might allow for drug holidays and reduction in the duration of therapy.

KEYWORDS:

• ASCT
• busulfan
• imetelestat
• interferon-α
• MPN

Article highlights box

• MPNs are incurable diseases without ASCT. Treatment is tailored to an individual patient’s symptoms and risk for disease progression as determined using a variety of stratification tools. MPNs almost uniformly necessitate prolonged continuous treatment with a variety of agents to maintain disease control.

• Treatment approaches that target and deplete the malignant clone and correct microenvironmental abnormalities might allow the reservoir of normal stem cells to predominate over malignant stem cells which would likely reduce the degree of MRD enabling drug holidays or potential cures.

• Busulfan and pegylated forms of IFN-α are two drugs currently available that can induce hematological remissions that can be sustained for prolonged time periods, thereby allowing for drug holidays.

• The use of pegylated forms of IFN has been associated with reductions in the driver mutation variant allele frequencies (VAFs) and occasional molecular remissions, which can be sustained even after drug interruption.

• Imetelstat, a telomerase inhibitor under clinical development, has been shown to lead to a significant prolongation of survival in very high-risk MF patients after a limited period of treatment.

• Novel therapeutic agents and combinations are being developed and evaluated with the goal of eliminating MRD and allowing prolonged drug holidays and possible cures.

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

This paper was not funded.