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Novel investigational approaches for high-risk genetic subsets of AML: TP53, KMT2A, FLT3

Kieran D Sahasrabudhe1, Alice S Mims1

  • 1The James Cancer Center, The Ohio State University, Columbus, OH.

Hematology. American Society of Hematology. Education Program
|December 9, 2022
PubMed

Insights

New treatments are needed for high-risk acute myeloid leukemia (AML) subtypes, including TP53-mutated AML, FLT3-ITD-mutated AML, and KMT2A-r AML, as current therapies offer poor prognoses and high relapse rates.

Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • The treatment landscape for acute myeloid leukemia (AML) is evolving, yet high-risk genetic subsets like TP53-mutated AML, FLT3-ITD-mutated AML, and KMT2A-r AML have poor prognoses.
  • Current intensive and targeted regimens, including venetoclax, show limited efficacy in TP53-mutated AML, with high post-transplant relapse rates.
  • Patients with FLT3-ITD-mutated AML and KMT2A-r AML also face suboptimal outcomes and lack established standards of care for relapsed/refractory disease.

Purpose of the Study:

  • To review current treatment strategies for three high-risk AML genetic subsets: TP53-mutated AML, FLT3-ITD-mutated AML, and KMT2A-r AML.
  • To discuss investigational agents under development for these challenging AML patient populations.
  • To highlight the unmet need for more effective therapies in specific high-risk AML groups.

Main Methods:

  • Literature review of current treatment approaches for AML.
  • Analysis of investigational agents targeting TP53-mutated AML, FLT3-ITD-mutated AML, and KMT2A-r AML.
  • Focus on agents in advanced stages of clinical development.

Main Results:

  • Prognosis remains poor for TP53-mutated AML despite available therapies and allogeneic stem cell transplantation.
  • FLT3-ITD-mutated AML patients experience high relapse rates after standard treatments and transplant.
  • KMT2A-r AML is associated with poor outcomes, and effective treatments for relapsed/refractory disease are lacking.

Conclusions:

  • There is a critical need for novel therapeutic strategies for high-risk AML genetic subsets.
  • Investigational agents show promise but require further development to improve outcomes for these patients.
  • Optimizing treatment for TP53-mutated, FLT3-ITD-mutated, and KMT2A-r AML is an ongoing challenge in the field.

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