Checkpoint inhibitors and acute myelogenous leukemia: promises and challenges

ABSTRACT

Introduction: Immunity, for treatment of acute myelogenous leukemia (AML), has been leveraged historically in the form of allogeneic stem cell transplantation. Checkpoint inhibitors (CPI) as positive modulators of immune response have been recent major breakthroughs in solid tumors.

Areas covered: Emerging concepts and clinical data with CPIs in acute Myeloid Leukemia – the focus of this review- will be discussed. CPIs can potentially be effective in absence of ‘actionable’ mutations and are expected to be effective against poor-risk AML. Immune inhibitory checkpoint molecules are upregulated in both de novo and relapsed AML. Similar data also suggest role of checkpoint molecules in mediating resistance particularly to hypomethylating agent (HMA) therapy, which can potentially be reversed by using checkpoint inhibitors.

Expert commentary: Ongoing clinical trials in combination with HMAs are showing early promise, with doubling of response than that seen in historic controls. The optimal combinations of CPIs and the optimal space that they will fit in the continuum of AML therapies need lot of in depth work.

KEYWORDS:

• Checkpoint inhibitors
• immunotherapy
• AML
• PD-1
• CTLA-4
• TIM-3
• nivolumab
• ipilimumab

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

Additional information

Funding

This study was supported in part by the MD Anderson Cancer Centre Support Grant (CCSG) CA016672, the MD Anderson Cancer Center Leukemia SPORE CA100632, the Charif Souki Cancer Research Fund and the MD Anderson Moon Shots Program.