Geriatric assessment in older patients with acute myeloid leukemia: A retrospective study of associated treatment and outcomes

doi:10.1016/j.leukres.2013.05.013

Leukemia Research

Volume 37, Issue 9, September 2013, Pages 998-1003

https://doi.org/10.1016/j.leukres.2013.05.013 Get rights and content

Abstract

We explored whether geriatric assessment variables predicted mortality in addition to known prognostic factors in 101 patients aged ≥65 with newly diagnosed AML. Baseline comorbidity score (HR = 1.92; 95%CI 1.18–3.11), difficulty with strenuous activity (HR = 2.18; 95%CI 1.19–4.00), and pain (HR = 2.17; 95%CI 1.19–3.97) were independent prognostic factors for greater risk of death in a multivariable model that included cytogenetic risk group. They remained independent predictors in the subset of patients with baseline ECOG PS 0-1. Our results support the use of geriatric assessment to better predict prognosis in older patients with AML, even among those with excellent functional status.

Introduction

Acute myeloid leukemia (AML) is a disease of older adults whose incidence will increase dramatically in coming decades due to population aging [1]. AML patients over age 65 have much worse prognosis than younger patients, with a five-year disease-specific survival of only 5% [2]. These poor outcomes are due to a combination of age-related changes in disease biology and clinical factors such as decreased physiologic reserve, functional impairment and frailty [3], [4], [5]. Previous work has identified age, performance status, comorbidity, and cytogenetic risk group as important prognostic factors in older patients with AML [6]. However, few studies have explored the relationship between geriatric assessment and AML outcomes.

Comprehensive geriatric assessment (CGA) is a systematic method of identifying multiple predictors of morbidity and mortality in older adults that may impact cancer treatment and is recommended for older cancer patients by NCCN guidelines [7]. This recommendation was in part based on a multicenter study demonstrating that a self-administered geriatric assessment identified important prognostic factors in cancer patients [8]. A geriatric evaluation includes assessment of multiple domains including comorbidity and physical, cognitive and social function. The feasibility of performing a modified CGA in older patients with AML has been demonstrated, but it is not yet known how this information predicts outcomes [9].

Careful assessment of the potential benefits and risks of therapy is particularly vital in AML, as intensive chemotherapy with cytarabine and an anthracycline is the only treatment that gives hope of long-term survival. Response to induction is poor among older adults and toxicity is substantially higher than in younger individuals, but selected patients can achieve remission and cure [10], [11], [12]. Patients who are not candidates for induction may benefit from non-intensive treatments such as hypomethylating agents, and some are best served by purely palliative approaches [13], [14]. However, it can be difficult to predict which older patients will benefit from chemotherapy using routine clinical and biological factors alone. Growing evidence suggests that measures of comorbidity and functional status may also be valuable prognostic factors in elderly patients with AML [15], [16], [17], [18]. We utilized prospectively collected quality of life data to evaluate the utility of geriatric factors as predictors of survival in older patients with AML across varying treatment intensities.

Section snippets

Data collection

We performed a retrospective cohort study of consecutive patients ≥65 years of age that presented to Dana-Farber Cancer Institute (DFCI) between 2006 and 2011 for evaluation of a new diagnosis of AML. At the DFCI, all new patients with hematologic malignancies are asked to participate in a research protocol that involves a baseline questionnaire and prospective collection of clinical data into the Cancer Research Information System (CRIS) database. CRIS includes information collected by trained

Results

Between 2006 and 2011, 368 patients 65 and older presented to the DFCI with a diagnosis of AML. Of these, 163 (44.3%) did not complete the new patient survey prior to hospitalization for AML, 62 (16.8%) received previous chemotherapy for AML, and 42 were missing information on key variables, leaving 101 patients for the analysis. Baseline characteristics of the cohort are listed in Table 1. Overall, the cohort was white (98%), had a performance status ≤1 (79.3%), and had ≤1 comorbidity (72.4%).

Discussion

In this retrospective study of older patients with AML, we found that baseline geriatric assessment variables added valuable prognostic information to conventional clinical and pathological predictors of mortality. The model that best predicted survival in our cohort included a disease-specific comorbidity score and self-reported measures of strenuous activity and pain in addition to cytogenetic risk group. Geriatric assessment variables remained independent predictors of mortality even among

Conflict of interest statement

The authors report no conflicts of interest or disclosures that could inappropriately influence their work on this project. Dr. Richard M Stone has served in a Consultant or Advisory Role for Genzyme^© and has received investigator-initiated research funding from Novartis^©. Dr. Daniel J DeAngelo has served in a consultant or advisory role for Novartis^©.

Acknowledgements

Funding source: Dr. Driver is funded by a Veterans’ Administration Career Development award. Alexander Sherman is funded by an American Federation for Aging Research Grant #1T35AG038027-02.

Author contributions: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data (AES, GM, KRF, DJD, GAA, DS, MW, RMS, JAD), (2) drafting the article or revising it critically for important intellectual content (AES, GM, KRF, DJD, GAA, DS, MW, RMS, JAD), (3)

References (33)

F.R. Appelbaum et al.
Age and acute myeloid leukemia
Blood
(2006)
L. Balducci et al.
Assessment and treatment of elderly patients with cancer
Surg Oncol
(2010)
A. Savic et al.
The hematopoietic cell transplantation comorbidity index is a predictor of early death and survival in adult acute myeloid leukemia patients
Leuk Res
(2012)
M.L. Sorror et al.
Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT
Blood
(2005)
H. Dohner et al.
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet
Blood
(2010)
U. Krug et al.
Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes
Lancet
(2010)
G. Juliusson et al.
Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry
Blood
(2009)
D. Feeny et al.
Hearing, mobility, and pain predict mortality: a longitudinal population-based study
J Clin Epidemiol
(2012)
H. Kantarjian et al.
Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia
Blood
(2010)
U.S. Interim Projections by Age, Sex, Race and Hispanic Origin, U.S.C., Bureau, Editor;...

N. Howlader et al.

SEER Cancer Statistics Review

(2012)

U. Wedding et al.

Impairment in functional status and survival in patients with acute myeloid leukaemia

J Cancer Res Clin Oncol

(2006)

S.K. Pal et al.

Evaluating the older patient with cancer: understanding frailty and the geriatric assessment

CA Cancer J Clin

(2010)

M.A. Sekeres et al.

Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome

Leukemia

(2004)

A. Hurria et al.

Developing a cancer-specific geriatric assessment: a feasibility study

Cancer

(2005)

H.D. Klepin et al.

The feasibility of inpatient geriatric assessment for older adults receiving induction chemotherapy for acute myelogenous leukemia

J Am Geriatr Soc

(2011)

Cited by (76)

Consolidation chemotherapy in AML: Are we playing with a full deck of cards?
2022, Best Practice and Research: Clinical Haematology
The safe diminution of leukemic cell numbers to a level such that the patient will not succumb to their disease has been an achievable, yet often elusive goal in AML. Disease heterogeneity based both on biological features as well as on patient characteristics such as age, exposure to prior to anti-cancer chemotherapy and co-morbidities play a role in an allowing the physician to predict which patient has a greater or lesser chance to be cured after a diagnosis of acute myeloid leukemia. Cure rates range from 95% in younger patients with non-high-risk acute promyelocytic leukemia to essentially zero in older adults with intrinsically resistant biologies such as complex karyotype and/or TP53 mutations. One unifying feature of all AMLs, however, is the notion that whatever initial therapy is used, while possible to eradicate all morphological evidence of disease in a sizeable fraction of patients, an initial cycle (or two) is not sufficient to yield a low enough disease burden to prevent eventual relapse. Thus, the application of additional chemotherapy after the initial complete remission is received (post-remission therapy generally or consolidation therapy if a myelointense approach is used) is absolutely required for the patient to have a reasonable chance at cure. The widely accepted principle of the need to provide post-remission therapy leads to multiple controversies pertaining to the appropriate intensity, drug choice, and duration of exposure to consolidation chemotherapy, which can range from repetitive cycles of non-intensive therapy, up to and including a myeloblative allogeneic stem cell transplant. In this review, both the principles and the individual strategies that can be used once remission is achieved, will be examined.
Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101
2022, Blood Advances
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 multisite trial. We conducted a companion study (CALGB 361101) to a randomized phase 2 trial (CALGB 11002) of adults ≥60 years and 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 in CALGB 11002, and 96 (52%) of them also enrolled in 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 (P < .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 (hazard ratio [HR], 3.5; confidence interval [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. This trial was registered at www.clinicaltrials.gov as #NCT01420926 (CALGB 11002).
Phase Ib trial of lenalidomide as post-remission therapy for older adults with acute myeloid leukemia: Safety and longitudinal assessment of geriatric functional domains
2022, Journal of Geriatric Oncology
Novel, non-cytotoxic agents are driving a paradigm shift for treatment of older adults with acute myeloid leukemia (AML). Older patients who initially receive intensive cytotoxic induction may choose to not proceed with cytotoxic consolidation therapy. Lenalidomide is an orally-administered immunomodulatory small molecule with activity in AML and a favorable safety profile in older adults with active leukemia. We conducted a phase Ib study of lenalidomide as post-remission therapy in older adults and assessed its impact on geriatric functional domains.
Participants were patients with AML over age 60 years who had undergone induction therapy and were poor candidates for cytotoxic consolidation. Lenalidomide was administered for 28 days in three dose cohorts. A Bayesian dose-escalation method determined cohort assignment and maximum tolerated dose (MTD). Geriatric assessment (GA) was performed before and after the cycle of lenalidomide.
Nineteen patients with median age 68 were treated with at least one 28-day course of lenalidomide. Dose-limiting toxicities were observed in three participants at 25 mg, zero participants at 35 mg, and one participant at 50 mg. MTD was 35 mg. Median relapse-free survival was 4.3 months. GA was completed before and after treatment in fifteen patients, demonstrating improved cognitive function and no changes in physical, psychological, or social function after lenalidomide.
Lenalidomide can be safely administered to older adults with AML with preservation of functional domains important to older patients. Serial GA can be performed in a novel drug study as a tool to characterize treatment tolerability.
Multisite 11-year experience of less-intensive vs intensive therapies in acute myeloid leukemia
2021, Blood
Citation Excerpt :
Still, future improvements in comorbidity assessment for AML to capture patients with more severe organ dysfunction could further improve stratifications for treatment outcomes. Another important measure of patient vulnerability is geriatric assessment including measures of frailty, physical, and cognitive function, which have been shown to predict survival.27-29 Accounting for comorbidities and geriatric assessment in the current study allowed for more informed and objective treatment comparisons.
Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.
Validation of the “fitness criteria” for the treatment of older patients with acute myeloid leukemia: A multicenter study on a series of 699 patients by the Network Rete Ematologica Lombarda (REL)
2021, Journal of Geriatric Oncology
Treatment of older patients with acute myeloid leukemia (AML) is still controversial. To facilitate treatment decisions, the “fitness criteria” proposed by Ferrara et al. (Leukemia, 2013), including age > 75 years, performance status and comorbidities, were verified retrospectively in 699 patients with AML (419 de-novo, 280 secondary AML), diagnosed at 8 Hematological Centers (REL).
Patients were categorized in FIT to intensive chemotherapy (i-T) (292, 42.5%), UNFIT to i-T (289, 42.1%), or unfit even to non-intensive therapy (non i-T) (FRAIL) (105, 15.3%). Biological characteristics and treatment actually received by patients [i-T, 274 patients (39.2%); non i-T, 134 (19.2%), best-supportive care (BSC), 291 (41.6%)] were recorded.
“Fitness criteria” were easily applicable in 98.1% of patients. Overall concordance between “fitness criteria” and treatment actually received by patients was high (79.4%), 76% in FIT, 82.7% in UNFIT and 80% in FRAIL patients. Fitness independently predicted survival (median survival: 10.9, 4.2 and 1.8 months in FIT, UNFIT and FRAIL patients, respectively; p = 0.000), as confirmed also by multivariate analysis. In FRAIL patients, survival with any treatment was no better than with BSC, in UNFIT non i-T was as effective as i-T and better than BSC, and in FIT patients i-T was better than non i-T or BSC. In addition, a non-adverse risk AML, an ECOG PS <2, and receiving any treatment other than BSC had a favorable effect on survival (p < 0.001).
These simple “fitness criteria” applied at the time of diagnosis could facilitate, together with AML biologic risk evaluation, the choice of the most appropriate treatment intensity in older AML patients.
Patient-Reported Outcomes as Independent Prognostic Factors for Survival in Oncology: Systematic Review and Meta-Analysis
2021, Value in Health
Assessment of patient-reported outcomes (PROs) in oncology is of critical importance because it provides unique information that may also predict clinical outcomes.
We conducted a systematic review of prognostic factor studies to examine the prognostic value of PROs for survival in cancer. A systematic literature search was performed in PubMed for studies published between 2013 and 2018. We considered any study, regardless of the research design, that included at least 1 PRO domain in the final multivariable prognostic model. The protocol (EPIPHANY) was published and registered in the International Prospective Register of Systematic Reviews (CRD42018099160).
Eligibility criteria selected 138 studies including 158 127 patients, of which 43 studies were randomized, controlled trials. Overall, 120 (87%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival. Lung (n = 41, 29.7%) and genitourinary (n = 27, 19.6%) cancers were most commonly investigated. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies. The EORTC QLQ-C30 questionnaire was the most frequently used measure, and its physical functioning scale (range 0-100) the most frequent independent prognostic PRO, with a pooled hazard ratio estimate of 0.88 per 10-point increase (95% CI 0.84-0.92).
There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. Further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.

View all citing articles on Scopus

View full text

Published by Elsevier Ltd.

Geriatric assessment in older patients with acute myeloid leukemia: A retrospective study of associated treatment and outcomes

Abstract

Introduction

Section snippets

Data collection

Results

Discussion

Conflict of interest statement

Acknowledgements

Blood

Surg Oncol

Leuk Res

Blood

Blood

Lancet

Blood

J Clin Epidemiol

Blood

SEER Cancer Statistics Review

Impairment in functional status and survival in patients with acute myeloid leukaemia

J Cancer Res Clin Oncol

Evaluating the older patient with cancer: understanding frailty and the geriatric assessment

CA Cancer J Clin

Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome

Leukemia

Developing a cancer-specific geriatric assessment: a feasibility study

Cancer

The feasibility of inpatient geriatric assessment for older adults receiving induction chemotherapy for acute myelogenous leukemia

J Am Geriatr Soc