Differential Impact of Prognostically Significant Gene Mutations in Acute Myeloid Leukemia (AML) Patients (Pts) Older Than 70 Years (y) Treated with Cytarabine-Based Induction Therapy

Introduction: AML is a heterogeneous disease of mainly older pts, with a median age of 68 y at diagnosis. Previous studies have shown that age is one of the most important prognosticators for overall survival (OS) of AML pts. In addition, several cytogenetic and molecular markers have been used for risk stratification of AML pts and to guide therapeutic decisions. However, the role of these established molecular marker (e.g. FLT3-ITD and NPM1 mutations) in pts aged ≥70 y is not fully understood. Aims: The goal of this study was to analyze the prognostic role of FLT3-ITD and other molecular markers in AML pts ≥70 y. We also compared this cohort with pts 60-69 y, who received a similar treatment, to identify potential differences between these age groups. Methods: We analyzed 269 de novo AML pts ≥70 y and 250 pts 60-69 y. All pts were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols that were based on standard intensity cytarabine/anthracycline induction followed by consolidation with varied chemotherapy regimens. None of the pts received an allogeneic stem cell transplant in first complete remission (CR). In pretreatment bone marrow or blood samples, the mutational status of 80 cancer- and leukemia-associated genes (Eisfeld et al., Leukemia 2017;31:2211) were determined using a targeted next-generation sequencing panel. All variants that occurred with variant allele fractions of .05). The pts’ pretreatment karyotypes were determined locally and reviewed centrally. Results: There were no significant differences in frequencies of any clinical or specific cytogenetic markers between AML pts ≥70 y and pts 60-69 y. Pts 60-69 y presented more often with Favorable-risk disease based on the European LeukemiaNet classification (Dohner et al. Blood 2017;129:424; 30% vs 23%, P Conclusions: Although pts aged ≥70 y had similar pretreatment clinical and cytogenetic features as pts 60-69 y, we showed that distinct differences can be found regarding prognosticators. Interestingly, we found that presence of a FLT3-ITD had no impact on outcome of pts ≥70 y, regardless of allelic ratio or presence of an additional NPM1 mutation. Only NPM1 mutations and complex karyotype had a prognostic impact on both age groups. Support: U10CA180821, U10CA180882 U24CA196171; https://acknowledgments.alliancefound.org; Clinicaltrials.gov Identifiers: NCT00048958 (CALGB-8461), NCT00899223 (CALGB 9665), and NCT00900224 (CALGB 20202) Download : Download high-res image (485KB) Download : Download full-size image Disclosures Walker: Vigeo Therapeutics: Consultancy; Karyopharm: Current Employment, Current equity holder in publicly-traded company. Blachly: AbbVie, AstraZeneca, KITE Pharma: Consultancy. Wang: Bristol Meyers Squibb (Celgene): Consultancy; Astellas: Consultancy; Jazz Pharmaceuticals: Consultancy; Macrogenics: Consultancy; PTC Therapeutics: Consultancy; Abbvie: Consultancy; Stemline: Speakers Bureau; Pfizer: Speakers Bureau; Genentech: Consultancy. Kolitz: Pfizer: Membership on an entity's Board of Directors or advisory committees; Magellan: Membership on an entity's Board of Directors or advisory committees. Powell: Rafael Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Novartis: Research Funding; Genentech: Research Funding. Stone: Gemoab: Consultancy; Syros: Consultancy; Arog: Consultancy, Research Funding; Celgene: Consultancy, Other; Macrogenics: Consultancy; Agios: Consultancy, Research Funding; Janssen: Consultancy; Aztra-Zeneca: Consultancy; Biolinerx: Consultancy; Trovagene: Consultancy; Daiichi-Sankyo: Consultancy; Argenix: Other; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB; Abbvie: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Astellas: Consultancy; Syntrix: Other: DSMB; Jazz: Consultancy; Stemline: Consultancy; Pfizer: Consultancy; Syndax: Consultancy, Research Funding. Byrd: Novartis: Research Funding; Acerta Pharma: Research Funding; Syndax: Research Funding; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Vincera: Research Funding; Kartos Therapeutics: Research Funding; Trillium: Research Funding; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau; Leukemia and Lymphoma Society: Other; Janssen: Consultancy. Eisfeld: Vigeo Therapeutics: Consultancy; Karyopharm: Current Employment, Current equity holder in publicly-traded company.