Determining treatment tolerance and fitness for intensive chemotherapy in older adults with AML: a call to action

Determining fitness for intensive chemotherapy in an older adult with acute myeloid leukemia (AML) is an unanswered age-old question. Geriatric assessment captures any variation in multidimensional health, which can influence treatment tolerance. A prospective study is necessary to validate fitness criteria, determine whether geriatric assessment-based fitness performs superiorly to other criteria, and what components of geriatric assessment are associated with treatment tolerance. A validation study should enroll diverse patients from both academic and community centers and patients receiving intensive and lower-intensity chemotherapy. Geriatric assessment should include at minimum measures of comorbidity burden, cognition, physical function, and emotional health, which in prior smaller studies have shown to be associated with mortality in AML. These assessments should be completed prior to or within a few days of initiation of chemotherapy to reduce the influence of chemotherapy on the assessment results. Treatment tolerance has been measured by rates of toxicities in patients with solid malignancies; however, during the initial treatment of AML, rates of toxicities are very high regardless of treatment intensity. Early or non-relapse mortality, frequently used in prior studies, can provide a highly consequential and easily identifiable measure of treatment tolerance. The key endpoint to assess treatment tolerance, thus, should include early or non-relapse mortality. Other endpoints may include decline in function and quality of life, and treatment modifications due to toxicities. Validating fitness criteria can guide treatment selection and supportive care interventions and are crucial to guide fitness-based trial eligibility, inform the interpretation of trial results, and facilitate drug labeling.