S130: NPM1 MUTATED AML: IMPACT OF CO-MUTATIONAL PATTERNS - RESULTS OF THE EUROPEAN HARMONY ALLIANCE

• DOI: 10.1097/01.hs9.0000843412.59637.1b
• Publication Date: 2022-06-23T07:01:49Z
• Authors: A. Hernández-Sánchez; Á. Villaverde-Ramiro; J. Martínez Elicegui; T. González; A. Benner; E. Sträng; G. Castellani; C. A. Heckman; J. Versluis; M. Abáigar; M. Sobas; R. Azibeiro; L. Tur; P. J. Valk; K. H. Metzeler; R. Ayala; D. Dall’Olio; J. Tettero; J. Martínez-López; H. Dombret; M. Pratcorona; F. Damm; K. I. Mills; J. Mayer; C. Thiede; M. T. Voso; G. F. Sanz; F. Calado; K. Döhner; V. I. Gaidzik; M. Heuser; T. Haferlach; A. T. Turki; D. Reinhardt; R. Villoria Medina; M. van Speybroeck; R. Schulze-Rath; M. Barbus; J. E. Butler; J. M. Hernández R...; B. J. Huntly; G. J. Ossenkoppele; H. Döhner; L. Bullinger
• Keywords: NPM1

Background: Acute myeloid leukemia (AML) is a heterogeneous disease in terms of clinical features, outcomes and genetics. While mutations NPM1 are usually considered as favorable prognostic marker, the vast majority patients carry several co-mutations that might influence prognosis. Therefore, better understanding NPM1mut AML mutational landscape warranted. The large cohort collected within European HARMONY Alliance provides an excellent basis for this purpose. Aims: To identify clinically significant co-mutational patterns order to establish revised risk stratification model. Methods: From database, total 1001 intensively treated were selected. Clinically evaluated using graphical created with Gephi tool confirmed by detailed survival analysis Kaplan-Meier Cox regression models. Finally, novel multi-state model was established. Results: study population included 57% females median age 53 years. Regarding ELN2017 classification, 68% classified into favorable, 29% intermediate 3% adverse groups. most frequent DNMT3A (54%), followed FLT3-ITD (38%). In total, 24% presented high allelic mutant-to-wildtype ratio ≥0.5 (FLT3-ITDhigh) while 14% had low <0.5 (FLT3-ITDlow). Other NRAS (21%), TET2 (20%) PTPN11 (15%). triple mutation pattern + FLT3-ITDhigh DNMT3Amut identified subgroup prognosis (2-year OS 25%), similar TP53mut. combination FLT3-ITDlow or DNMT3Awt associated 45% 53% respectively). Notably, NRAS, KRAS, RAD21 be OS. However, context these did not affect when present. This information summarized 3-category classification (Figure 1). group 2-year 73%, groups 54% 27% respectively (p<0.001). relapse free (RFS), reached group, it 23 months 6 It should noted 171 would according criteria, well 162 previously risk. our able reclassify 33% comparison criteria. Multivariate following independent factors: (taking reference, HR 1.6 2.7 p<0.001); secondary therapy-related (HR 1.8, p<0.001), WBC at diagnosis >100x103/μL 1.5, p<0.001) >60 years 1.4, p<0.001). Image:Summary/Conclusion: Analysis cohorts allows discovery co-mutation outcome. accordance, we propose new genetic identifies 3 different RFS. improves criteria correctly patients.