TEST:

FLT3 ITD MRD Assay

NPM1 MRD positive patients receiving nonmyeloablative conditioning or reduced-intensity conditioning (RIC) without melphalan (mel) had increased risk of relapse or death compared to patients receiving myeloablative conditioning or RIC with mel, regardless of FLT3-ITD co-mutational status (3yrs: relapse 87% vs 55%, P=0.006; OS 15% vs 42%, P=0.013). In patients with NPM1 mutated AML from the Pre-MEASURE study, we show that detection of residual NPM1 variants in pre-transplant blood during CR1 using a highly sensitive DNA-based assay is associated in a dose-dependent manner with a significantly increased risk of relapse and death after allo-HCT, which can be mitigated in part by conditioning regimen. In patients co-mutated for both FLT3-ITD and NPM1 at diagnosis, NPM1 should be prioritized as a target for NGS-MRD if only one test is available.

To our knowledge, our study is the first to assess the clinical impact of MRD detected below the clinically-validated limit of detection by ultra-sensitive NGS. Findings from our retrospective study were consistent with previously published data suggesting the presence of “high level” MRD (i.e. above the current clinically-validated limit of detection) is associated with increased risk of AML relapse in both NPM1 and FLT3-ITD mutated AML.

Patients achieving complete remission (CR) or CR with incomplete hematologic recovery (CRi) received ≤4 cycles of high-dose cytarabine + quizartinib (40mg/day) or placebo and/or allo-HCT followed by ~3 years of quizartinib continuation therapy (30-60mg/day) or placebo. Treatment with quizartinib prolonged OS in CR patients compared with placebo, irrespective of allo-HCT in CR1, and in patients undergoing allo-HCT in CR1, irrespective of pre- allo-HCT MRD status.

"Just launched! Invivoscribe’s FLT3 ITD MRD Assay for Acute Myeloid Leukemia (AML)...The FLT3 ITD MRD Assay is a targeted, deep-sequencing assay to identify internal tandem duplications (ITD), the most common mutation of the FLT3 gene. Unlike flow cytometry assays which require fresh sample and are highly subjective, this assay is designed for use with previously isolated DNA for scalable sample batching and an automated Linux-based software, circumventing the need for costly in-house bioinformatics expertise."

Patients achieving complete remission (CR) or CR with incomplete hematologic recovery (CRi) received up to 4 cycles of high-dose cytarabine plus quizartinib (40 mg/d) or placebo and/or allo-HCT followed by up to 3 years of quizartinib continuation therapy (30-60 mg/d) or placebo. Patients on quizartinib had longer OS than patients on placebo, irrespective of allo-HCT in CR1. Patients on quizartinib who underwent allo-HCT in CR1 had longer OS than patients on placebo, irrespective of pre–allo-HCT MRD status.