Mutation Patterns Identify Adult Patients with De Novo Acute Myeloid Leukemia (AML) Aged 60 Years or Older Who Respond Favorably to Standard Chemotherapy: an Analysis of Alliance Studies

Abstract Background: Despite changes in treatment regimens, the patient's age (and the corresponding treatment intensity) remains one of the most important prognostic factors in AML. Thus far, only 5-15% of AML patients aged ≥60 years (y) are cured with chemotherapy. Identification of patients who are more (or less) likely to respond to standard cytarabine/daunorubicin-based chemotherapy might help to enable early risk stratification toward alternative treatment regimens. Aims: To provide a comprehensive molecular profile of a large cohort of adults with de novo acute myeloid leukemia (AML) aged ≥60 y, and to determine if specific molecular and/or cytogenetic features could identify patients who are more likely to respond to standard chemotherapy. Methods: We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 patients aged ≥60 y with de novo AML and available cytogenetic data similarly treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology. Results: Overall, we detected 1377 mutations, with a median of 3 mutations per patient (range: 0-8). The outcome of the whole patient cohort was poor, with complete remission (CR) rate of 55% and disease-free (DFS) and overall survival (OS) 3y-rates of 14%. In multivariable analyses (MVA), mutated NPM1 was the only factor positively associated with achieving CR (P Summary: We identified combinations of mutations whose presence is associated with favorable outcome in older AML patients treated with standard chemotherapy. Patients with intermediate and adverse molecular features should be considered for alternative treatment regimens. Download : Download high-res image (186KB) Download : Download full-size image Figure 1 . Disclosures Stone: Otsuka: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Ono: Membership on an entity's Board of Directors or advisory committees; Orsenix: Membership on an entity's Board of Directors or advisory committees; Cornerstone: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Argenix: Other: DSMB; Arog: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Actinium: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Fujifilm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Seattle genetics: Membership on an entity's Board of Directors or advisory committees; Sumitomo: Membership on an entity's Board of Directors or advisory committees. Kolitz: Gilead, Magellan, Novartis, Pharmacyclics, and Seattle Genetics: Consultancy; Gilead, Magellan, and Novartis: Honoraria; Celgene, Jazz: Equity Ownership; Boehringer Ingelheim, Cantex, Erytech, and Millennium: Research Funding; Gilead, Novartis, and Seattle Genetics: Other: Travel Support. Powell: Rafael Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Byrd: Janssen: Research Funding; Genentech: Research Funding; Acerta Pharma: Research Funding; Pharmacyclics: Research Funding; The Ohio State University: Patents & Royalties: OSU-2S.