Quantum-First: Deep-Dive Analysis of FMS-like Tyrosine Kinase 3-Internal Tandem Duplication (FLT3-ITD) Detection Methods Utilized for Enrollment and Longitudinal MRD Detection in Newly Diagnosed (nd) Patients (pts) with FLT3-ITD-Positive (FLT3-ITD+) Acute Myeloid Leukemia (AML)
Abstract
Introduction
The phase 3 QuANTUM-First study (NCT02668653) showed that in nd FLT3-ITD+ AML pts, adding the oral, highly potent, selective, type 2 FLT3 inhibitor quizartinib to standard chemotherapy ± transplantation, followed by quizartinib or placebo monotherapy for up to 3 y, decreased relative risk of death by 22.4% vs placebo, with a generally manageable safety profile (PMID: 37116523). In QuANTUM-First, FLT3-ITD mutation status was determined using a FLT3-ITD mutation detection clinical trial assay (CTA). We describe concordance between the CTA and next-generation sequencing (NGS) measurable residual disease (MRD) assay in detecting the same FLT3-ITD sequences at screening and longitudinally. We provide FLT3-ITD detection results using the MRD assay in paired bone marrow (BM) aspirates and peripheral blood (PB) samples where available.
Methods
The CTA, developed by Navigate BioPharma Services, Inc., utilizes PCR and capillary electrophoresis (PCR + CE). FLT3-ITD mutations were detected in genomic DNA (gDNA) from nd FLT3-ITD+ AML pts by PCR with primers flanking exons 14 & 15 of the FLT3 gene. PCR products underwent fragment analysis on the ABI 3130xL Genetic Analyzer using ABI 3130xL Data Collection Software to resolve and generate different-sized PCR products. A DNA sample was considered CTA+ if the variant allele frequency (VAF; FLT3-ITD/total FLT3) was ≥3%. For the PCR + NGS MRD assay, gDNA from pts with composite complete remission (CRc = complete remission [CR] +…
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