Based on the results of a single-center phase II trial published by Bhatt et al in the American Journal of Hematology, pretreatment geriatric assessment in older adults with acute myeloid leukemia (AML) appeared to be feasible, to identify several functional impairments, to help guide the selection of treatment intensity, and result in low rates of early mortality.
Population and Treatment Strategy
A total of 73 patients with AML or a high-grade treatment-related myeloid neoplasm who were aged at least 60 years underwent geriatric assessments, including measures of comorbidity burden (Hematopoietic Cell Transplantation Comorbidity Index: score ≥ 3, 55%), self-reported physical function (Katz Activities of Daily Living Index: score ≤ 5, 29%; Lawton Instrumental Activities of Daily Living Index: score ≤ 7, 22%), objective physical function (Short Physical Performance Battery: score ≤ 9, 70%), and cognitive function (Montreal Cognitive Assessment: score ≤ 25, 64%). Any available genetic testing results were used for risk stratification into three categories: good (18%); intermediate (22%); and adverse (60%).
Patients who scored well on all geriatric assessments received intensive chemotherapy (good- or intermediate-risk: anthracycline plus cytarabine–based regimen [n = 4]; adverse-risk: liposomal daunorubicin/cytarabine [CPX-351; n = 4]). Low-intensity chemotherapy (azacitidine or decitabine and venetoclax: n = 43; decitabine or azacitidine alone [before venetoclax approval]: n = 18; other: n = 4) was administered in those who were deemed unfit or with adverse-risk disease not meeting the indication for CPX-351. The median time from enrollment to the initiation of therapy was 1 day (range: 0–13 days).
Broad eligibility criteria enabled enrollment of a population representative of that which is treated in real-world practices, the investigators highlighted.
Outcomes
A total of 52% of patients achieved either complete remission (40%) or complete remission with incomplete count recovery (12%) as the best response to study treatment. Other responses included morphologic leukemia-free state (2.8%) and resistant disease (35.6%); additionally, 9.6% of responses were not evaluable. The probabilities of achieving complete remission and complete remission with incomplete count recovery were 69.2%, 56.3%, and 45.5% for patients with good-, intermediate-, and adverse-risk disease, respectively; it was 50% for fit patients (treated with intensive chemotherapy) and 52.3% for their unfit counterparts.
With a median follow-up of 12 months, the mortality rate was 6.8% at 30 days and 21.9% (benchmark: 40%) at 90 days. The 1-year Kaplan-Meier estimated overall survival rate was 45.9%. The 30- and 90-day mortality rates were 0% and 7.7%, respectively, for the population with good-risk disease; of 13 such patients, 8 lived for 1 year and 6 lived for 2 years.
For fit and unfit patients, the mortality rates were 0% and 7.7% at 30 days and 12.5% and 23.1% at 90 days, respectively. The 1-year Kaplan-Meier estimated overall survival rate was 42.9% in fit patients and 46.3% in their unfit counterparts. AML was less frequently reported as the cause of death among fit vs unfit patients (40% vs 51%).
Allogeneic stem cell transplantation was subsequently performed in 41.1% of the population. A total of 75% and 37% of fit and unfit patients, respectively, underwent this procedure.
“Our study results demonstrate the success of broad eligibility criteria and academic-community collaboration in expanding access to clinical trials and in enrolling older adults who have multimorbidity or reside in rural areas,” the investigators concluded. “In this context, our approach to personalize selection of treatment intensity in older adults with AML, and our research design considerations, including broad eligibility criteria and collaboration with community oncology centers, can serve as a model for future trials that aim to answer issues specific to treatment selection in older adults with AML or other hematologic malignancies.”
They added, “While geriatric assessment results can provide an objective model to determine fitness for intensive chemotherapy, a randomized trial is necessary to confirm whether integrating geriatric assessment and genetic tests to select treatment intensity improves survival over the traditional approach.”
Vijaya R. Bhatt, MBBS, MS, of the University of Nebraska Medical Center, Omaha, is the corresponding author of the American Journal of Hematology article.
Disclosure: The study was funded by the National Institute of General Medical Sciences and the Fred & Pamela Buffett Cancer Center Support Grant from the National Cancer Institute. For full disclosures of the study authors, visit onlinelibrary.wiley.com.
