613. Acute Myeloid Leukemia: Molecular Mutations and Their Prognostic Implications

Sara Zarnegar-Lumley, Todd A. Alonzo, Megan Othus, et al.

Authors Conclusion from the Abstract: Analysis of this large patient cohort provides the most comprehensive description of IDH mutations in AML across the age spectrum. We confirm age-associated prevalence of IDH mutations and frequent co-occurrence with NPM1 mutation in all ages and in further combination with DNMT3A mutation in intermediate-aged adults. We definitively demonstrate that IDH mutation status is not an independent prognostic determinant of outcome in any age group. Co-occurrence of NPM1 and IDH mutations favorably impacts outcome in patients < 60 years of age with AML, particularly in the absence of DNMT3A mutation. Our data support that IDH inhibitors may be of particular interest in older adults and in patients <60 according to co-occurring NPM1 and DNMT3Amutations.

Badder Kattih, Amir Shirvani, Piroska Klement, et al.

Authors Conclusion from the Abstract: The presence of an IDH mutation in adult AML was associated with a higher prevalence of coronary artery disease and an exacerbated cardiotoxicity during anthracycline treatment, which was at least in part mediated by the oncometabolite R-2HG.

Nicholas J. Short, Guillermo Montalban-Bravo, Hyunsoo Hwang, et al.

Authors Conclusion from the Abstract: TP53mut VAF is highly prognostic for response, relapse and survival in pts with TP53­-mutated AML, particularly for those treated with conventional cytotoxic chemotherapy. Given the treatment-dependent impact of TP53mut VAF on clinical outcomes, VAF should be assessed when considering frontline therapy options. Further development of effective novel therapies is needed for this poor risk subgroup of pts.

Frank G. Rücker, Ling Du, Tamara J. Blätte, et al.

Authors Conclusion from the Abstract: In this cohort of 452 FLT3-ITD mutated AML pts treated within the RATIFY trial the negative prognostic impact of TKD1 IS was confirmed. A beneficial effect of midostaurin was only found for patients with JMDsole IS. In this subset, NPM1mut also exerted a strong beneficial effect.

Raffaele Palmieri, Francesco Buccisano, Alfonso Piciocchi, et al.

Authors Conclusion from the Abstract: In this GIMEMA AML1310 post-hoc analysis, we confirmed that the ELN2017 classification is able to accurately define pts that can benefit from different post-remission strategies. Specifically, AuSCT granted longer survival in FR pts, while for IR pts AuSCT and ASCT performed equally when minimal residual disease was used as a driver for opting between one of the two. In conclusion, ELN classification is a reliable grouping system that, combined with MRD assessment, helps addressing pts to the most appropriate treatment. Such an hypothesis will be prospectively challenged in the next GIMEMA trial AML1819.

Eline J.M. Bertrums, Jenny L. Smith, Rhonda E. Ries, et al.

Authors Conclusion from the Abstract: NUP98-X translocated pediatric AML patients represent a rare cohort with a high variability in both translocation partners and other clinical characteristics. Despite this heterogeneity, the OS of these patients is comparable to high-risk pediatric AML patients, which justifies a high-risk stratification of these patients and emphasizes the need for developing new treatment strategies. Further research within large patient cohorts is needed to investigate the biologic and clinical characteristics of these rare translocations and potential differences between the different NUP98-X fusion partners.