617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: MRD and Novel molecular Markers
Natasha S Anstee, Giovanna Pomilio, Mark Levis, et al.
Authors Conclusion from the Abstract: These studies demonstrate that in vivo SOR inhibited P-FLT3 to ≤15% during induction in the majority of cases and was associated with reduced relapse risk. Persistent FLT3-ITD MRD post-induction was associated with a high relapse risk in both treatment arms. For patients receiving SOR, failure to reduce P-FLT3 response to ≤15% was associated with a high risk of persistent FLT3-ITD MRD and clinical relapse.
Maximilian Stahl, Andriy Derkach, Christopher Famulare, et al.
Authors Conclusion from the Abstract: We show that transplanted AML pts with specific molecular mutations (RUNX1, SF3B1, and TP53) are unlikely to achieve MRD-CR/CRi after induction, consolidation or salvage therapy, while other mutations (NPM1, IDH1, KRAS) predict high rates of MRD- prior to alloSCT. Additional post-induction therapy may be advantageous for some MRD+ pts to achieve MRD- prior to alloSCT. Post-transplant OS is improved in pts who are MRD- at time of transplant, regardless of whether they required additional therapy beyond induction to achieve this state. AlloSCT is highly effective at eradicating MRD, but post-transplant MRD- is more durable in pts who are MRD- pre-alloSCT. Our results suggest that development of MRD-eradicating therapies has the potential to improve post-transplant outcomes and argues for innovative trials for pts with adverse molecular features currently unlikely to achieve MRD- pre alloSCT.
Rhonda E. Ries, Timothy Junius Triche Jr., Jenny L. Smith, et al.
Authors Conclusion from the Abstract: Here, by interrogation of the genome, phenome, transcriptome, and epigenome of mono7 AML a substantial phenotypic and prognostic heterogeneity exist defining a cohort of patients, regulated by genomic and epigenomic alterations. Further, the discovery of cryptic ALK fusions in mono7 presents a target for ALK inhibitors (FDA approved for non-small cell lung cancer) in this high-risk population.
Julia K. Herzig, Frank G. Rücker, Laura K. Schmalbrock, et al.
Authors Conclusion from the Abstract: In this first cohort of FLT3-ITD+ AML pts treated with intensive chemotherapy and midostaurin in the prospective AMLSG16-10 trial we could demonstrate that FLT3-ITD NGS-based MRD monitoring is feasible and represents a promising tool to evaluate therapy response and identification of pts at a higher risk of relapse. Further analysis of the study cohort is ongoing.
Abhishek Maiti, Courtney D. DiNardo, Sa A Wang, et al.
Authors Conclusion from the Abstract: Achievement of negative MRD status at 1- and 2-month time points is associated with significantly better OS and RFS in older pts with AML receiving frontline therapy with VEN and DEC.
Ing Soo Tiong, Richard Dillon, Adam Ivey, et al.
Authors Conclusion from the Abstract: We describe the natural history of patients with NPM1 mutated AML who remain MRD positive after completing intensive chemotherapy. Almost half either spontaneously achieve MRD-negativity or have stable low-level expression without relapse with minimum follow up of 8 mo. Patients with both FLT3-ITD and <4 log reduction in transcript levels at the end of therapy are at very high risk of disease progression and warrant consideration of pre-emptive treatment.