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2016-08-18T13:56:48.000Z

Precision medicine for Acute Myeloid Leukemia

Aug 18, 2016
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Modern treatment paradigms in Acute Myeloid Leukemia (AML) are becoming more focused on individualizing treatment for each particular patient. There are different approaches and factors to consider in order to achieve this, which in turn carry various potential benefits. For example, high sensitivity tracking of AML residual disease is not only used to ascertain the length of treatment, but it is also useful in determining the requirement for additional “maintenance therapy” after completion of standard treatment. C. Lai, et al, wrote an editorial reviewing precision medicine for AML. Their findings were first published as an Epub in Expert Review of Hematology in October 2015.

Here are the key benefits of this approach:

Targeting therapy to patient-specific somatic mutations

It is becoming widely accepted that identifying the location of mutations within the hierarchical clonal architecture of AML will be important to determine the most efficacious targets.

Ex-vivo veritas? Drug sensitivity and resistance testing

At present, it is not always possible to effectively design individualized patient therapy against a particular target or pathway. Instead, investigators have employed high-throughput methods to screen a host of drugs for the ability to preferentially destroy ex-vivo AML cells from a specific patient compared with normal bone marrow. The advantage of this approach relies on the fact that treatment can then be selected as a result of preclinical evidence for a specific patient. In addition, biomarkers can be identified.

High sensitivity measurements of residual disease burden and biology

Present AML response criteria are insufficient to stratify patients for risk of subsequent relapse and death. However, detailed sequential information regarding the amount of disease remaining to treat is equally as important as identifying the type of disease to be treated in any truly precision medicine strategy for AML. Also, the clonal composition of residual leukemia during or after treatment may provide predictive information in the form of biology, mutations or phenotype that are associated with response or treatment resistance to a therapy or combination therapy. 

In summary, precision medicine for AML involves more than choosing the correct drug, or correctly characterizing the malignant clone. This paradigm is entrenched on the need to select the right treatment, for the right patient, at the right time – and repeating this process while monitoring for changes in disease burden and biology over time.

 

  1. Lai C. et al. Precision medicine for acute myeloid leukemia. Expert Review of Hematology. 2016 Jan; 9(1):1-3. DOI: 10.1586/17474086.2016.1107471. Epub 2015 Oct 30.
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