Can increased immunogenicity in chronic myeloid leukemia improve outcomes?

ABSTRACT

Introduction: Chronic myeloid leukemia (CML) has long been thought to be the model disease for immunotherapy with its characteristic BCR-ABL fusion protein. Although targeted therapy using tyrosine kinase inhibitors (TKIs) is highly effective at inducing remission, most patients require life-long TKI to decrease the risk of relapse. In recent years, much effort has been devoted to finding ways to eliminate CML stem cells (LSCs); the source of disease persistence.

Areas covered: In this review, the authors present recent immunologic findings pertinent to CML, vaccinations targeting leukemia antigens, interferon combination therapies, and other emerging strategies aimed at increasing immunogenicity and improving outcomes in patients with CML. Recent publications and abstracts found in Pubmed and hematology/oncology meetings related to these topics were identified and incorporated into this review.

Expert commentary: Further understanding of the immune system and antigenic composition of LSCs has allowed for novel therapeutic development. Immunotherapies are effective at the malignant stem cell level and combining these approaches with TKI is a promising option. Despite ongoing challenges, it is increasingly recognized that a cure may be achievable through immunotherapies.

KEYWORDS:

• Chronic myeloid leukemia
• CML
• interferon with TKI
• immunogenicity
• leukemia-associated antigens
• tumor antigen-specific immunotherapy
• vaccines

Article highlights

• Tyrosine kinase inhibitors (TKIs) are not very effective against the quiescent chronic myeloid leukemia (CML) stem cells (LSCs).

• A large number of patients who achieved deep response initially and met criteria for TKI discontinuation experience molecular relapse soon after withdrawal.

• CML stem cells (LSCs) is thought to be the cause of relapse and increase understanding of the immune system and immunotherapies could potentially eliminate these cells and achieve the cure.

• Vaccinations targeting the characteristic BCR-ABL derived antigens, and other leukemia-associated antigens (LAAs) are promising immunotherapies for CML.

• Other approaches to increase immunogenicity include interferon-alpha and TKI combination therapy and immunomodulatory treatments such as ruxolitinib targeting the JAK/STAT pathway.

Declaration of interest

J Pinilla-Ibarz has received honoraria for consulting from Novartis, Bristol-Myers Squibb, and Takeda (speaker bureau). K Sweet has received honoraria for consulting and speaker bureau from Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has received honoraria and research funding from Novartis, BMS and Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.