Undetectable Measurable Residual Disease Is Associated With Improved Outcomes in AML Irrespective of Treatment Intensity

Authors

Alexandre Bazinet
Tapan Kadia
Nicholas J Short
Gautam Borthakur
Sa A Wang
Wei Wang
Sanam Loghavi
Jeffrey Jorgensen
Keyur Patel
Courtney DiNardo
Naval Daver
Yesid Alvarado
Fadi G Haddad
Sherry Pierce
Graciela Nogueras Gonzalez
Abhishek Maiti
Koji Sasaki
Musa Yilmaz
Philip Thompson
William Wierda
Guillermo Garcia-Manero
Michael Andreeff
Elias Jabbour
Marina Konopleva
Xuelin Huang
Hagop Kantarjian
Farhad Ravandi

Publication Date

7-11-2023

Journal

Blood Advances

Abstract

Acute myeloid leukemia (AML) can be treated with either high- or low-intensity regimens. Highly sensitive assays for measurable residual disease (MRD) now allow for a more precise assessment of response quality. We hypothesized that treatment (Rx) intensity may not be a key predictor of outcomes, assuming that an optimal response to therapy is achieved. We performed a single-center retrospective study including 635 patients with newly diagnosed AML responding to either intensive cytarabine/anthracycline-based chemotherapy (IA; n = 385) or low-intensity venetoclax-based regimens (LOW + VEN; n = 250) and who had adequate flow cytometry-based MRD testing performed at the time of best response. The median overall survival (OS) was 50.2, 18.2, 13.6, and 8.1 months for the IA MRD-, LOW + VEN MRD-, IA MRD+, and LOW + VEN MRD+ cohorts, respectively. The 2-year cumulative incidence of relapse (CIR) was 41.1%, 33.5%, 64.2%, and 59.9% for the IA MRD-, LOW + VEN MRD-, IA MRD+, and LOW + VEN MRD+ cohorts, respectively. The CIR was similar between patients within MRD categories irrespective of the treatment regimen received. The IA cohort was enriched for younger patients and favorable AML cytogenetic/molecular categories. Using multivariate analysis, age, best response (complete remission [CR]/CR with incomplete hematologic recovery/morphologic leukemia-free state), MRD status, and European LeukemiaNet (ELN) 2017 risk remained significantly associated with OS, whereas best response, MRD status, and ELN 2017 risk were significantly associated with CIR. Treatment intensity was not significantly associated with either OS or CIR. Achievement of MRD- CR should be the key objective of AML therapy in both high- and low-intensity treatment regimens.

Keywords

Humans, Retrospective Studies, Leukemia, Myeloid, Acute, Remission Induction, Disease-Free Survival, Prognosis, Recurrence, Neoplasm, Residual

Comments

Supplementary Materials

PMID: 36884300