High-Sensitivity Next-Generation Sequencing Mrd Assessment in All Identifies Patients at Very Low Risk of Relapse

Authors

Nicholas J Short
Hagop Kantarjian
Farhad Ravandi
Marina Konopleva
Nitin Jain
Rashmi Kanagal-Shamanna
Keyur P Patel
Walid Macaron
Tapan M Kadia
Sa Wang
Jeffrey L Jorgensen
Joseph D Khoury
Musa Yilmaz
Partow Kebriaei
Koichi Takahashi
Guillermo Garcia-Manero
Naval Daver
Sean M Post
Xuelin Huang
Steven M Kornblau
Sara Pelletier
Wilmer Flores
Jairo Matthews
Rebecca Garris
Elias Jabbour

Publication Date

7-12-2022

Journal

Blood Advances

Abstract

Measurable residual disease (MRD) is highly prognostic for relapse and overall survival (OS) in acute lymphoblastic leukemia (ALL), although many patients with apparent "MRD negativity" by standard assays still relapse. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay in 74 adults with ALL undergoing frontline therapy. Among remission samples that were MRD negative by multiparameter flow cytometry (MFC), 46% were MRD+ by the NGS assay. After 1 cycle of induction chemotherapy, MRD negativity by MFC at a sensitivity of 1 × 10-4 and NGS at a sensitivity of 1 × 10-6 was achieved in 66% and 23% of patients, respectively. The 5-year cumulative incidence of relapse (CIR) among patients who achieved MRD negativity by MFC at complete remission (CR) was 29%; in contrast, no patients who achieved early MRD negativity by NGS relapsed, and their 5-year OS was 90%. NGS MRD negativity at CR was associated with significantly decreased risk of relapse compared with MRD positivity (5-year CIR, 0% vs 45%, respectively; P = .04). Among patients who were MRD negative by MFC, detection of low levels of MRD by NGS identified patients who still had a significant risk of relapse (5-year CIR, 39%). Early assessment of MRD using a highly sensitive NGS assay adds clinically relevant prognostic information to standard MFC-based approaches and can identify patients with ALL undergoing frontline therapy who have a very low risk of relapse and excellent long-term survival.

Keywords

Acute Disease, Adult, Hematopoietic Stem Cell Transplantation, High-Throughput Nucleotide Sequencing, Humans, Neoplasm, Residual, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

DOI

10.1182/bloodadvances.2022007378

PMID

35533262

PMCID

PMC9278301

PubMedCentral® Posted Date

7-8-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes