Older patients with acute myeloid leukemia (AML) who undergo post-remission therapy may be at risk of poor survival if they present with impaired physical function and increased depressive symptoms at time of post-remission evaluation, according to a study published in Blood.
The study, led by Heidi Klepin, MD, of Wake Forest School of Medicine in North Carolina, demonstrates the value of geriatric assessment to strengthen risk stratification and identify vulnerabilities associated with AML in older adults. “Geriatric assessment measures add value by providing the opportunity to intervene with supportive care interventions and to calibrate prediction of treatment tolerance and benefit, which may yield both quality of life and survival benefits,” the investigators wrote.
Dr. Klepin and colleagues conducted a cohort analysis from a prospective observational study of 74 older adults (median age = 68.7 years) with newly diagnosed AML who underwent geriatric assessment during induction chemotherapy at a single center. Forty of these patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) after intensive induction chemotherapy and were considered eligible for post-remission consolidation chemotherapy. These 40 patients were included in the final analysis, which focused on the predictive value of geriatric assessment conducted at the time of post-remission evaluation.
Data from the geriatric assessments were obtained at the post-induction follow-up visit, which was around 8 weeks following induction hospital discharge. The assessment included the Modified Mini-Mental State Exam (MMSE), Center for Epidemiologic Studies Depression (CES-D) Scale, National Comprehensive Cancer Network (NCCN) Distress Thermometer, Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score, polypharmacy (≥5 prescription medications), Pepper Assessment Tool for Disability survey, basic and instrumental activities of daily living, Short Physical Performance Battery (SPPB), and hand grip strength.
Most patients (83%) received 2 or more cycles of post-remission chemotherapy.
Scores on the various geriatric assessment components are reported in the TABLE. Notably, 20% of patients had impairment on the MMSE and 26% and 36% of patients were considered impaired on the CES-D Scale and the NCCN Distress Thermometer, respectively. Larger proportions of patients reported impairment in physical function that affected their daily activities.
The median overall survival (OS) from the time of the post-remission assessment was 21.9 months. The investigators identified two assessment areas where impairment was significantly associated with worse OS: physical function and depressive symptoms.
For example, patients with an SPPB score of <9, representing physical function impairment, had a significantly worse OS compared with patients those with an SPPB score ≥9 (16.5 vs. 53.3 months, respectively; p=0.03). Patients with a CES-D score of ≥16 had a significantly worse median OS than individuals with a CES-D score of <16 (16.9 vs. 25.5 months; p=0.02).
Other components of geriatric assessment (cognitive impairment, distress, comorbidity, polypharmacy, and self-reported physical function) were not associated with survival, the authors noted.
In multivariate analyses, both an SPPB score of <9 and depressive symptoms at time of post-remission evaluation were associated with a higher risk of death (hazard ratios = 2.66 and 2.46, respectively).
“The post-induction period is a critical time for treatment decision-making as patients and physicians are often considering consolidation therapies such as cytarabine, bone marrow transplantation, or lower-intensity treatments to prolong remission,” the researchers concluded. “Our findings illustrate the value of repeat geriatric assessment to optimize risk stratification and better capture the dynamic vulnerabilities associated with AML and its treatment among older adults.”
Limitations of the study include the small number of patients, as well as the single-center design. In addition, the geriatric assessment used in this study did not incorporate other quality-of-life and disease components, including assessments of social support or delirium, the authors noted.
Saad M, Loh KP, Tooze JA, et al. Geriatric assessment and survival among older adults receiving post-remission therapy for acute myeloid leukemia. Blood. 2020 July 22. [Epub ahead of print]
This new study demonstrates that objective measurements of physical function and self-reported depression symptoms, assessed after patients with AML have attained remission, are associated with OS. Interestingly, in this analysis, cognitive impairment at post-remission evaluation was not associated with OS.
This study highlights the potential importance of tracking the geriatric assessment over time in patients with AML, but how often this assessment should be repeated during the illness course remains unknown. Nonetheless, it does appear that geriatric assessment after the initial induction phase and prior to receiving additional treatment has an important prognostic value. Geriatric assessment would be helpful to include in our discussion and decision-making with older patients regarding further treatment of AML.
I think the biggest limitation in this study is that it is unclear whether post-remission geriatric assessment adds further prognostic value over measuring the geriatric assessment at the time of initial diagnosis. Is the post-remission geriatric assessment identifying a different subset of patients who are at high risk of poor outcomes – i.e., patients whose condition deteriorated during induction – compared with the baseline geriatric assessment?
This study was limited by a small sample size, but ideally, in future studies, it would be helpful to see the prognostic value of serial measurements of certain domains of the geriatric assessment and whether changes from baseline to post-remission add additional information in this population.
Areej El-Jawahri, MD
Harvard Medical School
Massachusetts General Hospital