Background: Acute myeloid leukemia (AML) is a heterogenous disease that affects mostly older adults with varying baseline health and functional status. Treatment options have expanded for older adults, ranging from less intensive chronic therapies to intensive induction strategies with curative intent. Despite this, outcomes remain poor with advancing age due to underlying disease biology and variability in treatment tolerance. Reliance on chronological age alone, however, increases risks of both over- and under-treatment. Strategies to better characterize fitness in the context of therapy are needed to optimize decision-making and enhance clinical trial design. Summary: Geriatric assessment (GA) is a series of validated tools that evaluate multiple health and functional domains of an older adult including physical function, comorbidities, cognition, nutrition, psychological health, and social support. While studies of GA in AML remain limited, current evidence shows that it is feasible to perform GA among older adults starting therapy for AML. GA measures including those assessing physical function, cognition, and mood are associated with mortality and toxicity in both intensive and less intensive treatment settings. Key Messages: In this review, we discuss the existing evidence to support use of GA in AML and highlight implications for clinical practice and future research.

AML disproportionately affects older adults with a median age at diagnosis of 69 years [1]. The disease is genetically complex and more difficult to treat with increasing age, contributing to poor outcomes in comparison to younger patients [2, 3]. Five-year survival rates remain low (<10%) for older adults (defined as >60 years), with many older adults receiving no therapy for their disease despite evidence to support the potential benefits of treatment [3].

The treatment landscape for older adult patients with AML has evolved in recent years with effective lower intensity regimens entering the mainstream along with biology-driven therapies [4‒7]. As treatment options expand, the complexity of upfront treatment decision-making for older adults has increased. Specifically, the treatment landscape includes intensive therapies with curative intent as well as a growing number and combination of lower intensity treatments often administered chronically for disease control. Selecting the right therapy for the right patient at the right time requires an accurate understanding of both disease biology and patient characteristics that best represent “fitness” in older adults. Fit adults with older chronological age may be at risk for “under treatment” if age alone guides decision-making. Similarly, less fit patients exposed to therapies with higher toxicity risk may experience early complications when unmeasured vulnerabilities such as cognitive impairment are not recognized. There remains an unmet need to better characterize “fitness” in the context of treatment selection to enhance individualized decision-making and improve short- and long-term outcomes for older patients.

There is no gold standard assessment tool to characterize “fitness” in AML. Oncology performance status is routinely utilized in clinical trials and practice with evidence showing that poor performance status (i.e., Eastern Cooperative Oncology Group performance status >2) is a negative prognostic factor, indicating higher risk for morbidity and mortality. This scale, however, is not sensitive enough to identify relevant vulnerabilities among older adults with scores <2 [8]. Assessing comorbidities using tools such as the Hematopoietic Cell Transplantation Comorbidity Index can add data to inform prediction of early mortality or overall survival in the intensive and non-intensive setting [9‒12]. Recent clinical trials testing therapies for those “unfit for intensive treatment” utilize consensus criteria (Ferrara criteria) to define eligibility. These criteria include age (>75 years), major comorbidities, and performance status and have not yet been validated prospectively [13‒15]. The reliance on age alone as a surrogate for “fitness” remains a limitation. In this review, we will highlight works that have established the fundamental utility of geriatric assessment in the older adult AML population, reflect on how this knowledge has deepened, and explore the gaps that remain.

Geriatric assessment is a multi-dimensional characterization of health status that uses validated measures to assess domains including comorbidity burden, functional status, cognitive function, psychological health, nutritional status, polypharmacy, and social support. Although there are multiple different geriatric assessment protocols, the core domains include assessment of physical function utilizing both self-report and objective testing, assessment of multi-morbidity, evaluation of cognitive function, and assessment of emotional health. Cancer-specific geriatric assessment protocols were developed to streamline integration into cancer clinical trials and clinical practice [16, 17]. There is a growing evidence base, including studies in hematologic malignancies, that demonstrate the utility of pre-treatment geriatric assessment in predicting outcomes such as treatment toxicity, health care utilization, and survival in varied settings [18, 19].

Recently, multiple randomized trials have shown that pre-treatment geriatric assessment with management can decrease chemotherapy toxicity, lower hospitalization rates, improve communication, and enhance patient satisfaction [20‒22]. The American Society of Clinical Oncology (ASCO) published a guideline on practical assessment and management of older adults with cancer, first recommending geriatric assessment in 2018 with a recent update in 2023. The current guideline recommends that all patients with cancer age 65 years or older who are initiating systemic therapy complete a geriatric assessment with management plan prior to treatment. The guideline specifically recommends geriatric assessment to “identify vulnerabilities or impairments that are not routinely captured in oncology assessments” and help guide personalized cancer plan development [18, 23]. To facilitate implementation in practice, a standardized Practical Geriatric Assessment was recently published by the ASCO Guideline Expert Panel [23]. While the guideline recommendations include older adults with hematologic malignancies, older adults with acute myeloid leukemia were eligible for only one of the randomized trials, and total numbers included were small. Available evidence to support the utility of geriatric assessment in AML is largely derived from observational studies and described below.

Several prospective studies have shown that conducting pre-treatment geriatric assessment among older adults initiating intensive or less-intensive therapy for AML is feasible [8, 24, 25]. In a multi-site companion study (CALGB 361006) to a phase II trial of older adults with newly diagnosed FLT3-negative AML receiving intensive induction chemotherapy, median completion time of the entire geriatric assessment was 30 min, including both the healthcare provider-administered and patient self-assessment portions [24]. Providers reported no difficulty administering the assessments, and the vast majority of patients did not consider the assessments overly time consuming, showing it is feasible to incorporate geriatric assessment into multi-site AML trials that study intensive therapy regimens. The geriatric assessment measures used in these studies are largely delivered via surveys directly to patients with only the cognitive screen and physical performance testing (such as gait speed) administered by a member of the clinical team.

Table 1 describes published prospective studies utilizing geriatric assessment in AML. All of the studies used 60 years as the minimum age. Intensive chemotherapy was administered more often than low-intensity therapies. Common geriatric assessment domains evaluated were comorbidity, functional status, cognition, and depression, while some studies also evaluated nutrition, distress, social support, and quality of life. The specific tools used to assess each of these domains varied between trials and are detailed in Table 1.

Table 1.

Prospective studies investigating geriatric assessment in acute myeloid leukemia

Study informationPatients (n) and treatmentDesignDomainsToolsFindings
Klepin et al. [26n = 74, age ≥ 60 Single-center, prospective • Comorbidity • HCT-CI Impairments in cognition and physical performance are associated with worse overall survival 
USA; Blood 2013 Intensive chemotherapy for newly diagnosed AML • Functional status • PAT-D, SPPB, grip strength 
• Cognition • 3 MS 
• Depression • CES-D 
• Distress • Distress thermometer 
Deschler et al. [25n = 193, age ≥60 Multi-center, prospective • Comorbidity • HCT-CI, CCI Impairments in physical function and quality of life are predictive of overall survival 
Germany; Haematologica 2013 Any treatment for newly diagnosed AML or MDS • Functional status • KPS, ADL, TUG 
• Cognition • MMSE 
• Depression • GDS-15 
• Quality of life • EORTC QLQ-C30 
Klepin et al. [24n = 43, age ≥60 Multi-center, prospective • Comorbidity • HCT-CI, OARS Self-reported physical function, mental health, nutritional status, and social activity worsened after induction 
USA; JGO 2020 Intensive chemotherapy for newly diagnosed AML • Functional status • TUG, ADL, falls, KPS 
• Cognition • BOMC 
• Depression • MHI-17 
• Nutrition • BMI, % weight loss 
• Social support • MOS social activity 
Saad et al. [27n = 40, age ≥60 Single-center, prospective • Comorbidity • HCT-CI Depressive symptoms and impaired physical function are associated with worse overall survival 
USA; Blood 2020 After intensive induction therapy but prior to post-remission therapy • Functional status • SPPB, grip strength, ADL 
• Cognition • MMSE 
• Depression • CES-D 
• Distress • Distress Thermometer 
Min et al. [28n = 105, age ≥60 Single-center, prospective  • Functional status • SPPB, grip strength Physical impairment and cognitive dysfunction associated with nonfatal toxicities while physical impairment and depression associated with survival 
Korea; Blood 2020 Intensive chemotherapy for newly diagnosed AML • Cognition • MMSE-KC, KNU-DESC 
• Depression • GDS, PHQ-9 
• Nutrition • MNA 
• Distress • Distress Thermometer 
• Social support • OARS 
Ritchie et al. [9n = 82, age ≥60 Multi-center, prospective • Comorbidity • HCT-CI Higher comorbidity burden, impaired cognition, and lower quality of life are associated with shorter overall survival 
USA; Blood Adv 2022 Low intensity therapy for newly diagnosed AML • Functional status • TUG, ADL, falls, KPS 
• Cognition • BOMC 
• Depression • MHI-17 
• Nutrition • BMI, % weight loss 
• Social support • MOS social activity 
• Quality of life • EORTC QLQ-C30 
Study informationPatients (n) and treatmentDesignDomainsToolsFindings
Klepin et al. [26n = 74, age ≥ 60 Single-center, prospective • Comorbidity • HCT-CI Impairments in cognition and physical performance are associated with worse overall survival 
USA; Blood 2013 Intensive chemotherapy for newly diagnosed AML • Functional status • PAT-D, SPPB, grip strength 
• Cognition • 3 MS 
• Depression • CES-D 
• Distress • Distress thermometer 
Deschler et al. [25n = 193, age ≥60 Multi-center, prospective • Comorbidity • HCT-CI, CCI Impairments in physical function and quality of life are predictive of overall survival 
Germany; Haematologica 2013 Any treatment for newly diagnosed AML or MDS • Functional status • KPS, ADL, TUG 
• Cognition • MMSE 
• Depression • GDS-15 
• Quality of life • EORTC QLQ-C30 
Klepin et al. [24n = 43, age ≥60 Multi-center, prospective • Comorbidity • HCT-CI, OARS Self-reported physical function, mental health, nutritional status, and social activity worsened after induction 
USA; JGO 2020 Intensive chemotherapy for newly diagnosed AML • Functional status • TUG, ADL, falls, KPS 
• Cognition • BOMC 
• Depression • MHI-17 
• Nutrition • BMI, % weight loss 
• Social support • MOS social activity 
Saad et al. [27n = 40, age ≥60 Single-center, prospective • Comorbidity • HCT-CI Depressive symptoms and impaired physical function are associated with worse overall survival 
USA; Blood 2020 After intensive induction therapy but prior to post-remission therapy • Functional status • SPPB, grip strength, ADL 
• Cognition • MMSE 
• Depression • CES-D 
• Distress • Distress Thermometer 
Min et al. [28n = 105, age ≥60 Single-center, prospective  • Functional status • SPPB, grip strength Physical impairment and cognitive dysfunction associated with nonfatal toxicities while physical impairment and depression associated with survival 
Korea; Blood 2020 Intensive chemotherapy for newly diagnosed AML • Cognition • MMSE-KC, KNU-DESC 
• Depression • GDS, PHQ-9 
• Nutrition • MNA 
• Distress • Distress Thermometer 
• Social support • OARS 
Ritchie et al. [9n = 82, age ≥60 Multi-center, prospective • Comorbidity • HCT-CI Higher comorbidity burden, impaired cognition, and lower quality of life are associated with shorter overall survival 
USA; Blood Adv 2022 Low intensity therapy for newly diagnosed AML • Functional status • TUG, ADL, falls, KPS 
• Cognition • BOMC 
• Depression • MHI-17 
• Nutrition • BMI, % weight loss 
• Social support • MOS social activity 
• Quality of life • EORTC QLQ-C30 

HCT-CI, Hematopoietic Cell Transplant-Comorbidity Index; PAT-D, Pepper Assessment Tool for Disability; SPPB, Short Physical Performance Battery; 3 MS, Modified Mini-Mental state examination; CES-D, Center for Epidemiological Studies-Depression; CCI, Charlson Comorbidity Index; KPS, Karnofsky performance status; ADL, activities of daily living; TUG, timed up and go test; MMSE, Mini-Mental State Examination; GDS, Geriatric Depression Scale; EORTC QLQ-C30, European Organization for Research on Cancer Treatment Quality of Life Questionnaire; OARS, Older Americans Resources and Services; BOMC, Blessed Orientation-Memory-Concentration; MHI-17, Mental Health Inventory-17; BMI, body mass index; MOS, Medical Outcomes Study; MMSE-KC, Mini-Mental State examination (Korean version); KNU-DESC, Nursing Delirium Symptom Checklist (Korean version); PHQ-9, Patient Health Questionnaire-9; MNA, Mini Nutritional Assessment.

Pre-Treatment Assessment

Geriatric assessment can identify vulnerabilities that are not routinely captured in oncology assessments among older adults with AML. This information can enhance prediction of risks and benefits of treatment and inform targeted interventions to enhance resilience during treatment.

In a study of newly diagnosed older adults (age 60 and older) who were planning to initiate intensive induction chemotherapy, a high prevalence of impairments was detected in multiple geriatric assessment domains. Among the enrolled patients (N = 74), 42% had comorbidity, 29% had cognitive impairment, 72% reported limitations in physical function, 50% had impaired objective physical performance, and 40% screened positive for depressive symptoms despite most having a good oncology performance status [26]. In another study of newly diagnosed AML (N = 132) and myelodysplastic syndrome patients (N = 63) who underwent geriatric assessment irrespective of treatment received, 55% had functional impairments, 9% had cognitive impairment, and 14% had depression. In this study, more impairment was noted in patients receiving lower intensity therapies or best supportive care compared to intensive therapy [25]. While the prevalence of impairments differs by study in part due to varied assessment tools and populations, it seems clear that geriatric assessment detects variability in health status among older adults that is not captured by oncology performance status scales and chronological age.

Geriatric Assessment and Outcomes in the Intensive Induction Setting

Klepin and colleagues evaluated a cohort of 74 patients in the USA with newly diagnosed AML with geriatric assessment prior to initiation of induction chemotherapy. After multivariable analysis adjusting for age, gender, performance status, hemoglobin level, prior myelodysplastic syndrome, and cytogenetics, overall survival was lower in patients with impaired objectively measured physical function (hazard ratio (HR) 2.2, 95% confidence interval (CI): 1.1–4.6) and impaired cognition (HR 2.5, 95% CI: 1.2–5.5). Objectively measured physical function was assessed using the Short Physical Performance Battery (SPPB), a validated test which includes gait speed, balance testing, and repeat chair stands and is scored 0–12 (12 indicating highest function, <9 indicating impairment). Cognition was evaluated with the modified mini-mental state examination (3 MS) [26].

At a single institution in South Korea, Min and colleagues evaluated 105 newly diagnosed AML patients with geriatric assessment prior to intensive chemotherapy consisting of cytarabine and idarubicin [28]. The assessment included evaluations of physical function, cognition, depression, distress, nutrition, and social support. Impairment in physical function measured by SPPB was associated with grade 3 to 4 infections (p = 0.024) and renal failure (p = 0.013). Impaired cognition measured by MMSE was also associated with grade 3 to 4 infections (p = 0.044) and prolonged hospitalization (p = 0.005). In addition to demonstrating that geriatric assessment can predict these treatment toxicities, impaired physical function by SPBB and presence of depressive symptoms by Geriatric Depression Scale predicted lower survival. This study provided external validation for the association between pre-treatment physical performance, as assessed by the SPPB, and survival among an intensively treated older population. Importantly, the investigators showed that evaluating gait speed alone, a pragmatic clinical test, provides similar predictive utility [29].

Historically geriatric assessment is performed at the time of diagnosis, though Saad and colleagues explored a unique assessment time point after induction but prior to post-remission therapy [27], reporting that objectively measured physical function impairments and self-reported depressive symptoms were associated with shorter overall survival. Importantly, chronological age and performance status were not able to predict mortality in this population, once again illustrating the merits of a more robust multimodal assessment tool.

Based on current published data, high-yield geriatric assessment measures to assist in determining who is “fit” for intensive chemotherapy would include the SPPB or gait speed, a cognition screen, and evaluation of depressive symptoms. Larger studies validating these tools to identify those most likely to benefit from intensive treatment strategies are needed to standardize fitness assessments in trials and practice.

Geriatric Assessment and Outcomes in the Lower Intensity Induction Setting

Older adults with AML are receiving lower intensity therapies with increasing frequency. It is important to evaluate the utility of geriatric assessment within this treatment paradigm since the intensity and frequency of treatment differs and thresholds for determining tolerance to therapy may vary. One of the first studies to evaluate geriatric assessment in AML included 195 older adults (63 with myelodysplastic syndrome and 132 with AML) who received intensive chemotherapy (N = 75), low-intensity therapy (N = 73), or supportive care alone (N = 47) [25]. After multivariable analyses adjusted for performance status, cytogenetics, and bone marrow blast count, survival was lower in patients with greater comorbidity (per Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI); HR 2.0, 95% CI: 1.1–3.4), impaired activities of daily living (per Barthel Index; HR 2.5, 95% CI: 1.4–1.9), and self-reported fatigue (per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30; HR 1.8, 95% CI: 1.0–3.2). This study included a cohort of patients receiving non-intensive therapy but was limited in sample size with varied treatments allowed.

A more recent study, CALGB 361101, was a geriatric assessment companion study to a phase II treatment trial testing the efficacy of adding bortezomib to decitabine therapy among older adults with AML considered unfit for intensive therapy or who chose a less intensive approach. The goal of the companion study (N = 165) was to evaluate the predictive utility of geriatric assessment in patients treated with lower intensity therapy [9]. Geriatric assessment was administered prior to treatment and before each subsequent cycle of therapy, showing that greater comorbidity, worse cognition (measured by the Blessed Orientation Memory Concentration Test score ≥4), and lower EORTC global quality of life (QOL) scores at baseline correlated with shorter overall survival. For example, median overall survival was 10.4 months for those with better cognitive function (score <4) versus only 4.3 months for those with a worse score on the cognitive screen (≥4, p = 0.02). Furthermore, dependence in instrumental activities of daily living (IADL) and cognitive impairment were associated with 6-month mortality. This trial demonstrates that geriatric assessment can be embedded in larger cooperative group trials studying lower intensity AML therapies and that select measures are prognostic for worse survival in this setting.

While additional studies are needed that utilize the same geriatric assessment measures across treatment settings, available data suggests that tools predicting tolerance and benefit may differ based on the treatment setting. For example, cognitive impairment appears to be a relevant vulnerability in both the intensive and less intensive settings [30]. By contrast, IADL impairment may be more relevant for differentiating between those who are likely to benefit from hypomethylating agent-based treatment versus those who are unable to complete sufficient cycles of therapy [31]. A limitation to the current evidence is a lack of data specific to commonly used regimens including hypomethylating agent plus venetoclax and other biology-guided therapies.

Longitudinal geriatric assessments offer an opportunity to assess the impact of disease and treatment on health status during the course of AML survivorship [32]. Frailty is a dynamic state with patients both acquiring new vulnerabilities and demonstrating resilience and improvements in health status after initial AML therapy. Several prospective studies have evaluated the utility of repeated geriatric assessment among older adults treated for AML.

A prospective observational study of 49 older AML patients had geriatric assessment repeated approximately 8 weeks after intensive induction therapy [33]. Significant declines in self-reported and objectively measured physical function (SPPB and grip strength) were observed while cognitive function was preserved and emotional health (particularly distress) improved. In a sub-study of 20 patients from this cohort, inflammatory biomarkers were measured serially along with geriatric assessment at baseline and after induction [34]. Statistically significant correlations were observed between inflammatory biomarker levels (i.e., soluble tumor necrosis factor-α receptor 1, C-reactive protein, and IL-6 soluble receptor) and changes in physical and emotional health captured by geriatric assessment during the course of treatment.

A similar approach was taken in the multi-site geriatric assessment companion trial (CALGB 361006), evaluating change in geriatric assessment measures post-intensive induction among a subset (N = 43) of patients enrolled on a phase 2 trial testing the addition of sorafenib to intensive induction therapy for older adults with FLT3-mutated AML [24]. Self-reported physical function, mental health, nutritional parameters, and social activity measured by geriatric assessment all worsened after induction. In the same cohort, QOL, measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 questionnaire, improved significantly due to improved symptom control. These results show that information gained from geriatric assessment is complementary to global QOL assessment when characterizing how patients feel and function.

Another prospective observational study (N = 237) in AML patients evaluated changes in physical function and QOL after intensive induction chemotherapy and compared outcomes by age (less than or greater than 60 years) [35]. In this study, objective physical function was assessed by grip strength, 2-min walk test (2MWT), and timed chair stands pretreatment and at 7 time points over a year. Self-reported IADL limitations, QOL, and fatigue were assessed at the same timepoints. Results showed that IADL, grip strength, and the QOL domain of physical functioning decreased after treatment, nadiring around 2–3 months postinduction then gradually recovering to baseline by 1 year. Among patients who achieved remission, global QOL, fatigue, mood, 2MWT, and timed chair stands all improved steadily over time regardless of age, suggesting that disease status and therapy response may be associated with improved physical functioning and QOL.

In a small, single-institution, phase I drug trial of a novel post-remission treatment for older adults unfit to proceed with standard consolidation therapy, geriatric assessment was performed before and after one 28-day cycle of post-remission therapy [36]. Physical, psychological, and social function were preserved and cognition as measured by Blessed Orientation Memory Concentration Test improved at the second time point (p = 0.04). The authors suggest serial geriatric assessment can be a tool to characterize treatment tolerability in early phase trials for older adults.

We are learning that geriatric assessment results are dynamic as disease evolves and treatment accumulates, suggesting inherent value in repeating assessments over time. Studies attempting to gather geriatric assessment data over time can be hindered by general challenges associated with longitudinal clinical research including confounding comorbidities, disease evolution, treatment toxicity, changes in treatment, and study attrition. With respect to AML specifically, utilization of geriatric assessment as a dynamic marker of health and fitness may be more readily applicable to the intensive treatment paradigm for patients who are undergoing disease and clinical re-evaluation at specific timepoints (i.e., post-induction, pre-transplant). While the information gained can be equally important in the less intensive setting, determining when and how to reassess in this context may be more challenging. This was suggested by the high attrition rates in CALGB 361101 which attempted frequent serial assessments among patients receiving decitabine based treatment. Attrition largely precluded data capture and therefore limited any analysis of repeat geriatric assessment measures in this clinical trial ancillary study [9]. Pragmatic strategies to collect relevant data including brief patient report surveys with electronic data capture could be high yield in this setting, although a limitation to this approach is that the two most prognostic geriatric assessment parameters in AML, physical performance and cognitive testing, cannot be evaluated through an electronic survey.

Baseline/pre-treatment geriatric assessment should not only be used as a screening tool to identify vulnerabilities, but it should also prompt healthcare practitioners to intervene. Examples of addressing impairments would include providing mobility equipment when falls are identified, delivering nutritional supplements to underweight patients, and offering therapy or community support to patients with depression or social isolation.

Physical activity interventions have been formally studied in older adults with AML. The addition of supervised exercise during induction chemotherapy in the inpatient setting was shown to improve patient aerobic fitness, grip strength, and lower body strength in comparison with those not participating in structured exercise in a non-age-selected cohort (18–80 years) [37]. Physical activity interventions tailored to older adults receiving intensive induction therapy have been piloted and show feasibility and promising preliminary data to support benefits, although randomized trial efficacy data are lacking [38, 39]. More recently, Loh and colleagues developed a mobile phone application to improve exercise adherence in a group of older patients with myeloid neoplasms receiving outpatient chemotherapy [40]. Average daily number of steps increased from 2,848 to 3,184 after the intervention and participants were noted to enjoy the application, the social interaction it provided, and its flexibility.

In addition to guiding supportive care interventions like exercise, information obtained through geriatric assessment can influence treatment decisions for older adults with AML. A phase II drug trial in older adults with AML used geriatric assessment to allocate patients between intensive chemotherapy (for the 61% of patients deemed “fully or partially fit”) or best supportive care (for 39% deemed “frail”) [41]. A multidimensional geriatric assessment evaluating physical function, comorbidities, and geriatric syndromes was administered to stratify fitness groups. Median overall survival of intensively treated patients was 11.4 months compared with 1.5 months for the best supportive care group. Interestingly, there was no difference between the “fully fit” and “partially fit” group in terms of duration of hospitalization, infection rate, or induction death rate, suggesting that geriatric assessment was able to accurately identify a group of moderately fit older adults who would benefit from treatment without experiencing increased toxicity compared to their more evidently fit peers.

Another innovative trial at a single center used geriatric assessment along with AML genetic risk categories to guide treatment decisions between intensive chemotherapy and lower intensity therapy [42]. If a patient was found to have impairments beyond the predefined cut points in any single category of comorbidity burden, physical function, or cognitive function, they were deemed “vulnerable” and received low intensity therapy. If they were found to be “fit” in the above geriatric assessment categories, patients with good or intermediate risk genetics based on 2017 European Leukemia Net criteria received chemotherapy, while patients with high-risk genetic features received either low intensity therapy or chemotherapy. This trial provides a model for using geriatric assessment to define fitness in older adults with AML and guide treatment decision-making. In addition, it demonstrates how geriatric assessment data can be interpreted alongside disease biology information like genetics to build precise and personalized treatment plans.

A qualitative analysis of factors that influence treatment decision-making in older adults with AML identified four broad categories: patient-related, disease/treatment-related, physician-related, and organization-related considerations [43]. Geriatric assessment provides robust patient-related information and can better guide complex patient-centered communication regarding disease and treatment options. Use of geriatric assessment data to support conversations regarding goal-concordant care is an area of active research in AML [44].

Despite the feasibility of geriatric assessment demonstrated in AML clinical trials and its increasing use in that setting, recent survey data of oncology providers in general indicate that there are several issues with implementing geriatric assessment in clinical practice [45]. Only 53% of the 1,277 providers surveyed were aware of the ASCO guideline recommending geriatric assessment to be performed in older adults with cancer, suggesting provider awareness is the first barrier. Of note, the original ASCO guideline was published in May 2018 and the survey was conducted between April and June 2019. The percentage of aware providers would likely be higher if a similar survey were conducted today after several years have passed and an updated guideline has been published, but it is clear that dissemination of data and recommendations supporting the use of geriatric assessment in oncology patients is a challenge to more widespread implementation in clinical practice. Among providers who were aware of the guideline, 69% assess functional status, 45% assess comorbidity, and 37% assess cognition versus 50%, 24%, and 15% among providers unaware of the guideline, respectively. These differences demonstrate the importance of geriatric assessment awareness but also show that overcoming the awareness hurdle does not always translate to implementation. Guideline-aware providers most frequently cited logistical barriers to performing geriatric assessment, including time (82%) and support staff limitations (77%), but also acknowledged educational barriers such as lack of training or knowledge (58%) and lack of awareness of validated tools (57%).

Finding solutions for these various impediments to geriatric assessment implementation is a difficult task. Time constraints can be managed at least in part through the use of patient survey data collection whenever possible as opposed to provider-administered assessments, acknowledging that physical performance and cognitive testing must be performed in person. Another mechanism to reduce the time burden is to streamline the assessment process at an institutional level by, for example, establishing standards for which patients will be assessed, when and where the assessments will take place, who will gather the information, and who will interpret the data. An ideal scenario would be to have an individual familiar with older adults and the geriatric assessment gather the information and the treating providers or a dedicated geriatric oncology clinic interpret the data. Best practices of implementation could be showcased in future trials and become more widely used if successful.

In general, we recommend the ASCO Practical Geriatric Assessment, which was developed to address barriers to clinical implementation including time constraints yet is still comprehensive in assessing physical function, functional status, comorbidities, cognition, psychological function, social support, and nutritional status [23]. Gait speed and cognitive screening are included in this assessment which are key domains for AML pre-treatment screening. Clinical trials are likely to design geriatric assessments based on this going forward, though Table 1 demonstrates that variation between geriatric assessment domains and component tools in AML trials has varied only minimally. In a resource-limited clinical setting, we recommend assessing as many of the domains shown to be most prognostic in AML – physical function, cognitive function, and comorbidities – as possible to assist in detecting subtle impairments in this vulnerable population.

Next steps to optimize use of geriatric assessment to improve care for older adults include incorporating standardized geriatric assessment measures into therapeutic clinical trials to better characterize health status of enrolled patients, validate predictors of treatment tolerance, and facilitate “fitness-based” risk stratification in trial design. Studies testing geriatric assessment-guided management to include targeted supportive care interventions to enhance resilience and goal-concordant care are needed. Finally, testing implementation strategies to facilitate use of geriatric assessment in clinical practice will enhance access to aging-specialized care beyond clinical trials.

Geriatric assessment is a tool that can uncover health and functional impairments, predict outcomes, and guide supportive care planning in older adults with AML. It has consistently been shown to be more useful in achieving these goals than chronological age or performance status alone. Available evidence supports the use of measures of physical function, comorbidity, cognition, and emotional health to enhance decision-making and guide supportive care.

The authors have no conflicts of interest to declare.

Funding was received from Wake Forest Baptist Comprehensive Cancer Center’s National Cancer Institute Cancer Center Support Grant P30CA012197.

J.D.W. prepared and reviewed the manuscript. H.D.K. edited and reviewed the manuscript.

1.
1988-2014 (SEER 13); last accessed 2.19.19. Available from: https://seercancergov/indexhtml/2019. https://seer.cancer.gov/faststats/.
2.
Thein
MS
,
Ershler
WB
,
Jemal
A
,
Yates
JW
,
Baer
MR
.
Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades
.
Cancer
.
2013
;
119
(
15
):
2720
7
.
3.
Sekeres
MA
,
Guyatt
G
,
Abel
G
,
Alibhai
S
,
Altman
JK
,
Buckstein
R
.
American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults
.
Blood Adv
.
2020
;
4
(
15
):
3528
49
.
4.
DiNardo
CD
,
Jonas
BA
,
Pullarkat
V
,
Thirman
MJ
,
Garcia
JS
,
Wei
AH
.
Azacitidine and venetoclax in previously untreated acute myeloid leukemia
.
N Engl J Med
.
2020
;
383
(
7
):
617
29
.
5.
Lancet
JE
,
Uy
GL
,
Cortes
JE
,
Newell
LF
,
Lin
TL
,
Ritchie
EK
.
CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia
.
J Clin Oncol
.
2018
;
36
(
26
):
2684
92
.
6.
Wei
ASS
,
Strickland
SA
,
Hou
JZ
,
Fiedler
W
,
Lin
TL
,
Walter
RB
.
Venetoclax with low-dose cytarabine Induces rapid, deep, and durable responses in previously untreated older adults with AML Ineligible for intensive chemotherapy
.
Blood
.
2018
132
Suppl 1
284
.
7.
DiNardo
CD
,
Stein
EM
,
de Botton
S
,
Roboz
GJ
,
Altman
JK
,
Mims
AS
.
Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML
.
N Engl J Med
.
2018
;
378
(
25
):
2386
98
.
8.
Klepin
HD
,
Geiger
AM
,
Tooze
JA
,
Kritchevsky
SB
,
Williamson
JD
,
Ellis
LR
.
The feasibility of inpatient geriatric assessment for older adults receiving induction chemotherapy for acute myelogenous leukemia
.
J Am Geriatr Soc
.
2011
;
59
(
10
):
1837
46
.
9.
Ritchie
EK
,
Klepin
HD
,
Storrick
E
,
Major
B
,
Le-Rademacher
J
,
Wadleigh
M
.
Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101
.
Blood Adv
.
2022
;
6
(
12
):
3812
20
.
10.
Walter
RB
,
Othus
M
,
Borthakur
G
,
Ravandi
F
,
Cortes
JE
,
Pierce
SA
.
Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment
.
J Clin Oncol
.
2011
;
29
(
33
):
4417
23
.
11.
Giles
FJ
,
Borthakur
G
,
Ravandi
F
,
Faderl
S
,
Verstovsek
S
,
Thomas
D
.
The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia
.
Br J Haematol
.
2007
;
136
(
4
):
624
7
.
12.
Sorror
ML
,
Storer
BE
,
Fathi
AT
,
Gerds
AT
,
Medeiros
BC
,
Shami
P
.
Development and validation of a novel acute myeloid leukemia-composite model to estimate risks of mortality
.
JAMA Oncol
.
2017
;
3
(
12
):
1675
82
.
13.
Ferrara
F
,
Barosi
G
,
Venditti
A
,
Angelucci
E
,
Gobbi
M
,
Pane
F
.
Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on a new tool for therapy decision making
.
Leukemia
.
2013
;
27
(
5
):
997
9
.
14.
Desprez
C
,
Riou
J
,
Peterlin
P
,
Marchand
T
,
Couturier
MA
,
Villate
A
.
Comparison of scoring systems evaluating suitability for intensive chemotherapy in adults with acute myeloid leukemia-a Grand Ouest against Leukemia (GOAL) study
.
Leukemia
.
2022
;
36
(
10
):
2408
17
.
15.
Palmieri
R
,
Othus
M
,
Halpern
AB
,
Percival
MEM
,
Godwin
CD
,
Becker
PS
.
Accuracy of SIE/SIES/GITMO consensus criteria for unfitness to predict early mortality after intensive chemotherapy in adults with AML or other high-grade myeloid neoplasm
.
J Clin Oncol
.
2020
;
38
(
35
):
4163
74
.
16.
Hurria
A
,
Cirrincione
CT
,
Muss
HB
,
Kornblith
AB
,
Barry
W
,
Artz
AS
.
Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401
.
J Clin Oncol
.
2011
;
29
(
10
):
1290
6
.
17.
Hurria
A
,
Gupta
S
,
Zauderer
M
,
Zuckerman
EL
,
Cohen
HJ
,
Muss
H
.
Developing a cancer-specific geriatric assessment: a feasibility study
.
Cancer
.
2005
;
104
(
9
):
1998
2005
.
18.
Mohile
SG
,
Dale
W
,
Somerfield
MR
.
Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology
.
J Clin Oncol
.
2018
Jco2018788687
.
19.
Scheepers
ERM
,
Vondeling
AM
,
Thielen
N
,
van der Griend
R
,
Stauder
R
,
Hamaker
ME
.
Geriatric assessment in older patients with a hematologic malignancy: a systematic review
.
Haematologica Jun
.
2020
;
105
(
6
):
1484
93
.
20.
Mohile
SG
,
Epstein
RM
,
Hurria
A
.
Communication with older patients with cancer using geriatric assessment: a cluster-randomized clinical trial from the national cancer Institute community oncology research program
.
JAMA oncology
.
2019
;
7
:
1
9
.
21.
Mohile
SG
,
Mohamed
MR
,
Xu
H
,
Culakova
E
,
Loh
KP
,
Magnuson
A
.
Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study
.
Lancet
.
2021
;
398
(
10314
):
1894
904
.
22.
Li
D
,
Sun
CL
,
Kim
H
,
Soto-Perez-de-Celis
E
,
Chung
V
,
Koczywas
M
.
Geriatric assessment-driven intervention (GAIN) on chemotherapy-related toxic effects in older adults with cancer: a randomized clinical trial
.
JAMA Oncol
.
2021
;
7
(
11
):
e214158
.
23.
Dale
W
,
Klepin
HD
,
Williams
GR
,
Alibhai
SMH
,
Bergerot
C
,
Brintzenhofeszoc
K
.
Practical assessment and management of vulnerabilities in older patients receiving systemic cancer therapy: ASCO guideline update
.
J Clin Oncol
.
2023
;
41
(
26
):
4293
312
.
24.
Klepin
HD
,
Ritchie
E
,
Major-Elechi
B
,
Le-Rademacher
J
,
Seisler
D
,
Storrick
L
.
Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: report of CALGB 361006 (Alliance)
.
J Geriatr Oncol
.
2020
;
11
(
1
):
107
13
.
25.
Deschler
B
,
Ihorst
G
,
Platzbecker
U
,
Germing
U
,
März
E
,
de Figuerido
M
.
Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome
.
Haematologica
.
2013
;
98
(
2
):
208
16
.
26.
Klepin
HD
,
Geiger
AM
,
Tooze
JA
,
Kritchevsky
SB
,
Williamson
JD
,
Pardee
TS
.
Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia
.
Blood
.
2013
;
121
(
21
):
4287
94
.
27.
Saad
M
,
Loh
KP
,
Tooze
JA
,
Pardee
TS
,
Ellis
LR
,
Powell
BL
.
Geriatric assessment and survival among older adults receiving post-remission therapy for acute myeloid leukemia
.
Blood
.
2020
;
136
(
23
):
2715
9
.
28.
Min
GJ
,
Cho
BS
,
Park
SS
,
Park
S
,
Jeon
YW
,
Shin
SH
.
Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML
.
Blood
.
2022
;
139
(
11
):
1646
58
.
29.
Klepin
HD
.
Toward consensus on geriatric assessment in AML
.
Blood
.
2022
;
139
(
11
):
1605
6
.
30.
Magnuson
A
,
Van der Walde
N
,
McKoy
JM
,
Wildes
TM
,
Wong
ML
,
Le-Rademacher
J
.
Integrating geriatric assessment measures into national cancer Institute clinical trials
.
J Natl Cancer Inst Monogr
.
2022
;
2022
(
60
):
142
50
.
31.
Molga
A
,
Wall
M
,
Chhetri
R
,
Wee
LY
,
Singhal
D
,
Edwards
S
.
Comprehensive geriatric assessment predicts azacitidine treatment duration and survival in older patients with myelodysplastic syndromes
.
J Geriatr Oncol
.
2019
;
11
(
1
):
114
20
.
32.
Lin
RJ
,
Klepin
HD
.
Evidence-Based Minireview: longitudinal geriatric assessment in quality care for older patients with hematologic malignancies
.
Hematol Am Soc Hematol Educ Program
.
2019
;
2019
(
1
):
59
62
.
33.
Klepin
HD
,
Tooze
JA
,
Pardee
TS
,
Ellis
LR
,
Berenzon
D
,
Mihalko
SL
.
Effect of intensive chemotherapy on physical, cognitive, and emotional health of older adults with acute myeloid leukemia
.
J Am Geriatr Soc
.
2016
;
64
(
10
):
1988
95
.
34.
Loh
KP
,
Tooze
JA
,
Nicklas
BJ
,
Kritchevsky
SB
,
Williamson
JD
,
Ellis
LR
.
Inflammatory biomarkers, geriatric assessment, and treatment outcomes in acute myeloid leukemia
.
J Geriatr Oncol
.
2020
;
11
(
3
):
410
6
.
35.
Alibhai
SM
,
Breunis
H
,
Timilshina
N
,
Brignardello-Petersen
R
,
Tomlinson
G
,
Mohamedali
H
.
Quality of life and physical function in adults treated with intensive chemotherapy for acute myeloid leukemia improve over time independent of age
.
J Geriatr Oncol
.
2015
;
6
(
4
):
262
71
.
36.
Woods
JD
,
Zeidner
JF
,
Van Deventer
HW
,
Jamieson
K
,
Matson
M
,
Zhang
J
.
Phase Ib trial of lenalidomide as post-remission therapy for older adults with acute myeloid leukemia: safety and longitudinal assessment of geriatric functional domains
.
J Geriatr Oncol
.
2022
;
13
(
4
):
499
504
.
37.
Alibhai
SM
,
Durbano
S
,
Breunis
H
,
Brandwein
JM
,
Timilshina
N
,
Tomlinson
GA
.
A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy
.
Leuk Res
.
2015
;
39
(
11
):
1178
86
.
38.
Klepin
HD
,
Danhauer
SC
,
Tooze
JA
,
Stott
K
,
Daley
K
,
Vishnevsky
T
.
Exercise for older adult inpatients with acute myelogenous leukemia: a pilot study
.
J Geriatr Oncol
.
2011
;
2
(
1
):
11
7
.
39.
Klepin
HD
,
Tooze
JA
,
Rejeski
J
,
Mihalko
S
,
Pardee
TS
,
Demark-Wahnefried
W
.
Tailoring a physical activity intervention to older adults receiving intensive chemotherapy for acute myeloid leukemia (AML): one size does not fit all
.
J Geriatr Oncol
.
2022
;
13
(
4
):
511
5
.
40.
Loh
KP
,
Sanapala
C
,
Watson
EE
,
Jensen-Battaglia
M
,
Janelsins
MC
,
Klepin
HD
.
A single-arm pilot study of a mobile health exercise intervention (GO-EXCAP) in older patients with myeloid neoplasms
.
Blood Adv
.
2022
;
6
(
13
):
3850
60
.
41.
Capelli
D
,
Saraceni
F
,
Fiorentini
A
,
Chiarucci
M
,
Menotti
D
,
Poloni
A
.
Feasibility and outcome of a phase II study of intensive induction chemotherapy in 91 elderly patients with AML evaluated using a simplified multidimensional geriatric assessment
.
Adv Ther
.
2020
;
37
(
5
):
2288
302
.
42.
Bhatt
VR
,
Wichman
C
,
Al-Kadhimi
ZS
,
Koll
TT
,
Fisher
AL
,
Mahato
RI
.
Integrating geriatric assessment and genetic profiling to personalize therapy selection in older adults with acute myeloid leukemia
.
J Geriatr Oncol
.
2022
;
13
(
6
):
871
4
.
43.
Loh
KP
,
Abdallah
M
,
Kadambi
S
,
Wells
M
,
Kumar
AJ
,
Mendler
JH
.
Treatment decision-making in acute myeloid leukemia: a qualitative study of older adults and community oncologists
.
Leuk Lymphoma
.
2021
;
62
(
2
):
387
98
.
44.
Watson
E
,
Sanapala
C
,
Cortes
AM
,
Klepin
HD
,
Wittink
M
,
Norton
S
.
Adapting a patient-centered communication tool for older patients with acute myeloid leukemia and their oncologist
.
Blood Adv
.
2022
;
6
(
21
):
5707
10
.
45.
Dale
W
,
Williams
GR
,
R MacKenzie
A
,
Soto-Perez-de-Celis
E
,
Maggiore
RJ
,
Merrill
JK
.
How Is Geriatric Assessment Used in Clinical Practice for Older Adults With Cancer? A Survey of Cancer Providers by the American Society of Clinical Oncology
.
JCO Oncol Pract
.
2021
;
17
(
6
):
336
344
.