Checkpoint inhibitors and acute myelogenous leukemia: promises and challenges.
Mansour AlfayezGautam BorthakurPublished in: Expert review of hematology (2019)
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.
Keyphrases
- acute myeloid leukemia
- stem cell transplantation
- dna damage
- cell cycle
- allogeneic hematopoietic stem cell transplantation
- high dose
- liver failure
- immune response
- clinical trial
- bone marrow
- respiratory failure
- big data
- electronic health record
- acute lymphoblastic leukemia
- cell proliferation
- small molecule
- intensive care unit
- oxidative stress
- drug induced
- aortic dissection
- mesenchymal stem cells
- diffuse large b cell lymphoma
- randomized controlled trial
- hepatitis b virus
- machine learning
- optical coherence tomography
- clinical practice
- data analysis
- replacement therapy
- study protocol
- extracorporeal membrane oxygenation
- cell therapy
- mechanical ventilation
- smoking cessation