Characterizing "fitness" in the context of therapeutic decisions for older adults with acute myeloid leukemia (AML) is challenging. Available evidence is strongest in identifying those older adults who are frail at the time of diagnosis by characterizing performance status and comorbidity burden. However, many older adults with adequate performance status and absence of major comorbidity are "vulnerable" and may experience clinical and functional decline when stressed with intensive therapies. More refined assessments are needed to differentiate between fit and vulnerable older adults regardless of chronologic age. Geriatric assessment has been shown to add information to routine oncology assessment and improve risk stratification for older adults with AML. This review highlights available evidence for assessment of "fitness" among older adults diagnosed with AML and discusses future treatment and research implications.
Learning Objective• To recognize patient characteristics that influence treatment tolerance for older adults receiving chemotherapy for AMLThe majority of patients with acute myeloid leukemia (AML) are age 65 or older, with approximately one-third of patients Ն75 years of age at diagnosis. 1 Despite this, the optimal treatment for older patients remains unclear. Compared with middle-aged patients, older adults (typically defined as Ն60 or 65 years) experience shortened survival and increased treatment-associated morbidity. [1][2][3] For example, population-based data from the United States (Surveillance Epidemiology End Results, SEER) highlight the age-related survival disparity. Rates of 5-year survival from time of diagnosis decline from 39% to 8.5% to Ͻ2% for people Ͻ65, 65-74, and Ն75 years of age, respectively. 1 Older adults are more likely to experience treatment-related death than younger patients, ranging from 10% to 30% in many clinical trials. [2][3][4] Chronologic age, however, is a surrogate measure for both changes in tumor biology (conferring treatment resistance) and patient characteristics (affecting treatment tolerance). Both tumor biology and physiologic reserve vary widely among older adults of similar chronologic age, necessitating individualized assessment strategies.
Controversy of intensive therapy for older adults with AMLConcerns regarding efficacy and toxicity of standard treatments have resulted in Ͻ40% of older adults receiving chemotherapy for AML in the United States. 5 Despite poor outcomes for older adults in aggregate, clinical trial and observational data show that chemotherapy can improve survival for selected patients, even those Ͼ80 years of age. 4-7 A landmark study comparing intensive induction in a randomized fashion to supportive care demonstrated a small but measurable survival advantage for patients 65 years of age and older. 4 Survival has improved over time in both observational data and clinical trials, although the magnitude of improvement declines with increased age. 1,5,[8][9][10][11] Observational data also suggest that the effect of induction th...