Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101

Abstract

Geriatric assessment (GA) predicts survival among older adults with acute myeloid leukemia (AML) treated intensively. We evaluated the predictive utility of GA among older adults treated with low intensity therapy on a multi-site trial. We conducted a companion study (CALGB 361101) to a randomized phase 2 trial (CALGB 11002) of adults >=60 years considered "unfit" for intensive therapy, testing the efficacy of adding bortezomib to decitabine therapy. On 361101, GA and quality of life (QOL) assessment was administered prior to treatment and every other subsequent cycle. Relationships between baseline GA and QOL measures with survival were evaluated using Kaplan Meier estimation and Cox Proportional Hazards models. One-hundred sixty-five patients enrolled on CALGB 11002 and 96 (52%) of them also enrolled on 361101 (median age, 73.9 years). Among participants, 85.4% completed ≥1 baseline assessment. In multivariate analyses, greater comorbidity (Hematopoietic Cell Transplantation-specific Comorbidity Index >3), worse cognition (Blessed Orientation Memory Concentration score > 4), and lower European Organization for Research and Treatment of Cancer global QOL scores at baseline were significantly associated with shorter overall survival (OS) (p<0.05 each) after adjustment for Karnofsky Performance Status, age and treatment arm. Dependence in Instrumental Activities of Daily Living and cognitive impairment were associated with 6 month mortality (HR 3.5, CI 1.2-10.4, and HR 3.1 CI 1.1-8.6 respectively). GA measures evaluating comorbidity, cognition, and self-reported function were associated with survival and represent candidate measures for screening older adults planned to receive lower intensity AML therapies.

Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management

“…Although there is no standardization of type of assessment, 204 a geriatric assessment can reveal vulnerabilities that are not detected in routine clinical practice 205 and predicts morbidity and mortality 206,207 . The prognostic value of geriatric assessment was also seen in older patients treated with lower intensity regimens 208 as well as intensive chemotherapy, and can aid in predicting non‐fatal toxicities during induction 209 . In a randomized trial, standard oncological consultation with additional geriatrician consultation versus without was associated with higher rates of end‐of‐life and goals of care discussion, in addition to being valued by 63%–88% of clinicians as beneficial 210 …”

Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update

“…While the evidence is strongest for GAM for those with solid tumor malignancies, there is evidence supporting them in those with hematologic malignancies in addition to patients with lymphoma. [72][73][74] Additionally, as pointed out in the clinical implications section, the value of GA for identifying agingassociated concerns and communicating with patients and families is important for all older adults with cancer and is well established. The questions regarding other systemic therapies, such as the rapidly growing field of immunotherapy, are still being developed.…”

Geriatric Assessment in Acute Myeloid Leukemia

“…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.…”

“…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.…”

“…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][10][11][12]. Recent clinical trials testing therapies for those "unfit for intensive treatment" utilize consensus criteria (Ferrara criteria) to define eligibility.…”