Fried Frailty Phenotype Predicts Mortality for Newly Diagnosed Older Patients with Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Introduction: Older patients with high-risk myeloid malignancies are now eligible for either induction chemotherapy (IC) or novel treatment strategies including liposomal cytarabine and daunorubicin (Vyxeos) or hypomethylating agent (HMA)/venetoclax. Vyxeos and HMA/venetoclax may be associated with less early mortality, but no trials have demonstrated significantly less mortality compared to IC. In this context, we need a better tool to determine a patient's risk of early mortality by strategy in order to inform therapy selection for older patients. The current methods to assess a patient's fitness for IC are the Eastern Cooperative Oncology Group (ECOG) or Karnofsky Performance Status (KPS) assessments, clinician subjective evaluations [i.e. gestalt (CG)], and often age itself (>75-80 years). None of these include objective measures of fitness. The Fried frailty phenotype (FP) uses both subjective (exhaustion and activity level) and objective measures (weight loss, gait speed, and grip strength) of frailty to categorize patients into fit, pre-frail, and frail. We hypothesized that FP would correlate with early mortality in this population and could be used to guide initial treatment selection. Methods: From September, 2018 to June, 2019 we prospectively enrolled 30 patients age 60 years or older with newly diagnosed, untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) on an ongoing institutional review board approved clinical trial. We performed FP, CG, hematopoietic cell transplantation-comorbidity index (HCT-CI), and ECOG assessments on all patients prior to initiation of any therapy for their high grade myeloid disease. The primary endpoints were 60 and 100-day mortality. Results: Median patient age and follow up were 70.9 (range 61-82) years and 111 days, respectively. Patients had high-risk disease features as shown in Table 1, with the vast majority of AML patients being adverse risk by European Leukemia Network criteria and all MDS patients being high or very high-risk by the Revised International Prognostic Scoring System. The most common molecular mutations were TP53, ASXL1, RUNX1, IDH1/2, FLT3, and DNMT3A. IC consisting of either 7+3 or Vyxeos was used in 11 patients, HMA alone or in combination in 16, targeted therapy with enasidenib alone in 1, and best supportive care (BSC) in 2 (Table 1). Four patients who were frail by FP received IC (3 with Vyxeos). By FP assessments, 17% of patients were fit (score 0), 33% w