High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse

• DOI: 10.1182/bloodadvances.2022007378
• Publication Date: 2022-05-09T18:33:16Z
• Authors: Nicholas J. Short; Hagop Kantarjian; Farhad Ravandi; Marina Konopleva; Nitin Jain; Rashmi Kanagal-Sh...; Keyur P. Patel; Walid Macaron; Tapan M. Kadia; Sa Wang; Jeffrey L. Jorgensen; Joseph D. Khoury; Musa Yilmaz; Partow Kebriaei; Koichi Takahashi; Guillermo Garcia-...; Naval Daver; Sean M. Post; Xuelin Huang; Steven M. Kornblau; Sara Pelletier; Wilmer Flores; Jairo Matthews; Rebecca Garris; Elias Jabbour
• Keywords: Minimal Residual Disease; Cumulative incidence; Negativity effect

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 sensitive next-generation sequencing (NGS) MRD assay 74 adults ALL undergoing frontline therapy. Among remission samples that were negative multiparameter flow cytometry (MFC), 46% MRD+ NGS assay. After 1 cycle induction chemotherapy, negativity MFC at sensitivity × 10-4 10-6 was achieved 66% 23% patients, respectively. The 5-year cumulative incidence (CIR) among who complete (CR) 29%; contrast, no early relapsed, their OS 90%. CR associated significantly decreased risk compared positivity (5-year CIR, 0% vs 45%, respectively; P = .04). MFC, detection low levels identified had significant 39%). Early assessment using adds clinically relevant information to MFC-based approaches can identify therapy have very excellent long-term survival.