Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia

Maximilian Stahl*, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A. Patel, Sheng F. Cai, Linde A. Miles, Robert L. Bowman, Mark B. Geyer, Andrew Dunbar, Zachary D. Epstein-Peterson, Erin McGovern, Jessica Schulman, Jacob L. Glass, Justin TaylorAaron D. Viny, Eytan M. Stein, Bartlomiej Getta, Maria E. Arcila, Qi Gao, Juliet Barker, Brian C. Shaffer, Esperanza B. Papadopoulos, Boglarka Gyurkocza, Miguel Angel Perales, Omar Abdel-Wahab, Ross L. Levine, Sergio A. Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S. Tallman, Mikhail Roshal, Aaron D. Goldberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD− remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD− remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD− remission. Patients with fewer individual clones were more likely to achieve MRD− remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD− after induction or later MRD− after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalAmerican Journal of Hematology
Volume98
Issue number1
DOIs
StatePublished - Jan 2023

ASJC Scopus subject areas

  • Hematology

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