TY - JOUR
T1 - Mutation- and MRD-informed treatments for transplant-ineligible patients
AU - Lachowiez, Curtis A.
AU - DiNardo, Courtney D.
N1 - Publisher Copyright:
Copyright © 2024 by The American Society of Hematology.
PY - 2024/11/25
Y1 - 2024/11/25
N2 - 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.
AB - 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.
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U2 - 10.1182/hematology.2024000540
DO - 10.1182/hematology.2024000540
M3 - Review article
C2 - 39644009
AN - SCOPUS:85212011081
SN - 1520-4391
VL - 2024
SP - 168
EP - 177
JO - Hematology. American Society of Hematology. Education Program
JF - Hematology. American Society of Hematology. Education Program
IS - 1
ER -