Mutation- and MRD-informed treatments for transplant-ineligible patients

Curtis A. Lachowiez, Courtney D. DiNardo

Research output: Contribution to journalReview articlepeer-review

Abstract

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups. Furthermore, the simultaneous discovery of resistance mechanisms to targeted therapies and AZA-VEN has enabled the identification of patient subgroups with inferior outcomes, leading to the development, of new risk-stratification models and clinical investigations incorporating targeted therapies using an HMA-VEN-based platform. Treatments inclusive of IDH1, IDH2, FLT3, and menin inhibitors combined with HMA-VEN have additionally demonstrated safety and high rates of efficacy in early-phase clinical trials, suggesting these regimens may further improve outcomes within select subgroups of patients with AML in the near future. Additional studies defining the prognostic role of measurable residual disease following VEN-based treatment have further advanced prognostication capabilities and increased the ability for close disease monitoring and early targeted intervention prior to morphologic relapse. This review summarizes these recent developments and their impact on the treatment and survival of transplant-ineligible patients living with AML.

Original languageEnglish (US)
Pages (from-to)168-177
Number of pages10
JournalHematology. American Society of Hematology. Education Program
Volume2024
Issue number1
DOIs
StatePublished - Nov 25 2024

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Mutation- and MRD-informed treatments for transplant-ineligible patients'. Together they form a unique fingerprint.

Cite this