Impact of Measurable Residual Disease Clearance Kinetics in Patients With AML Undergoing Intensive Chemotherapy

Authors

Wei-Ying Jen
Koji Sasaki
Farhad Ravandi
Tapan M Kadia
Sa A Wang
Wei Wang
Sanam Loghavi
Naval G Daver
Courtney D DiNardo
Ghayas C Issa
Hussein A Abbas
Cedric Nasnas
Alex Bataller
Samuel Urrutia
Omer S Karrar
Sherry Pierce
Hagop M Kantarjian
Nicholas J Short

Publication Date

2-25-2025

Journal

Blood Advances

Abstract

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) was 73 months, 22 months, and 5 months for the MRD Neg/Neg, Pos/Neg, and Pos/Pos groups, respectively (P < .01). There was a significant difference between the Neg/Neg and Pos/Neg groups (P = .05), suggesting benefit to early MRD negativity. The median overall survival (OS) was 81 months, 40 months, and 9 months, respectively (P < .01), but the difference between Neg/Neg and Pos/Neg was not statistically significant (P = .19). Landmark analysis demonstrated the benefit of stem cell transplant (SCT), particularly in Neg/Neg intermediate-risk AML (median RFS, not reached vs 15 months; P < .01). On multivariable analysis, MRD Pos/Neg was independently associated with a worse RFS than Neg/Neg (hazard ratio, 1.73; 95% confidence interval, 1.09-2.75; P = .02) but not for OS (P = .15). In conclusion, undetectable flow MRD after induction is associated with better RFS than undetectable MRD achieved later during consolidation. SCT benefited patients with intermediate-risk AML, regardless of MRD kinetics.

Keywords

Humans, Neoplasm, Residual, Leukemia, Myeloid, Acute, Male, Female, Middle Aged, Adult, Aged, Retrospective Studies, Young Adult, Prognosis, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Kinetics, Treatment Outcome

DOI

10.1182/bloodadvances.2024013826

PMID

39631072

PMCID

PMC11869955

PubMedCentral® Posted Date

12-7-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes