TEST:

NPM1 Mutation 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.

"Kronos Bio...and Invivoscribe, a global provider of diagnostic kits and services for oncology, today announced their agreement to develop a companion diagnostic (CDx) for use with Kronos Bio's investigational therapy, entospletinib....The diagnostic will screen for the NPM1 mutation, which is present in approximately one-third of all patients with AML....Entospletinib is currently being studied in the Phase 3 AGILITY registrational study, with data anticipated in second half of 2023."