Geriatric assessment and survival among older adults receiving postremission therapy for acute myeloid leukemia.
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ABSTRACT:
SUBMITTER: Saad M
PROVIDER: S-EPMC7735162 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Geriatric assessment and survival among older adults receiving postremission therapy for acute myeloid leukemia.
Saad Mohammed M Loh Kah Poh KP Tooze Janet A JA Pardee Timothy S TS Ellis Leslie R LR Powell Bayard L BL Bhave Rupali Roy RR Geiger Ann M AM Williamson Jeff D JD Kritchevsky Stephen S Klepin Heidi D HD
Blood 20201201 23
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Project description: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).
| S-EPMC9631575 | biostudies-literature
Project description:The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management.
| S-EPMC6070943 | biostudies-literature
Project description:Acute myeloid leukemia (AML) presents therapeutic challenges in older adults because of high-risk leukemia biology conferring chemoresistance, and poor functional status resulting in increased therapy-related toxicities. Recent FDA approval of 8 new drugs for AML has increased therapeutic armamentarium and also provides effective low-intensity treatment options. Rational therapy selection strategies that consider individual's risk of therapy-related toxicities and probability of disease control can maximize benefits of available treatments. Studies have demonstrated that fitness level, measured by geriatric assessment can predict therapy-related toxicities, whereas cytogenetic and mutation results correlate with the probability of responses to standard chemotherapy. We are approaching an era when we move from "one size fits all" approach to personalized therapy selection based on geriatric assessment, genetic and molecular profiling.
| S-EPMC6481658 | biostudies-literature
Project description:IntroductionSurvival benefit associated with intensive over low-intensity chemotherapy in older adults with acute myeloid leukemia (AML) is controversial. Geriatric assessment and genetic risk categories correlate with survival following intensive chemotherapy in older adults with AML and can guide treatment selection.Materials and methodsIn a single-center trial, we integrated both geriatric assessment, and genetic risk categories to personalize selection of intensive versus low-intensity chemotherapy in older adults ≥60 years with AML (NCT03226418). In the present report, we demonstrate feasibility of this approach.ResultsBroad eligibility criteria and co-management of patients with community oncologists allowed enrollment of 45% of all patients with AML treated at our center during the study period. The median time from enrollment to therapy initiation was two days (range 0-9). Over half of the trial patients had a score of ≥3 on hematopoietic cell transplantation comorbidity index, impairment in physical function (Short Physical Performance Battery), and Montreal Cognitive Assessment. Three fit patients received intensive chemotherapy, whereas other patients received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 3.7% (95% confidence interval [CI] 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). One-year overall survival was 66% (95% CI 60-87%).DiscussionOur data demonstrate the feasibility of integrating geriatric assessment in precision oncology trials to define fitness for intensive chemotherapy. Broad eligibility criteria and academic-community collaboration can expand access to clinical trials.
| S-EPMC9482687 | biostudies-literature
Project description:ObjectivesTo investigate changes in inflammatory biomarkers during induction therapy for older adults with acute myeloid leukemia (AML) and their associations with geriatric assessment (GA) measures and outcomes.MethodsThis was a single institution ancillary study to a prospective observational study (N = 20 consecutive adults aged ≥60 with newly diagnosed AML who received induction chemotherapy). Biomarkers (Interleukin-6 [IL-6], IL-6 soluble receptor [IL-6 sR], tumor necrosis factor alpha [TNFα], TNFα soluble receptor 1 [TNFα sR1], interleukin-3 [IL-3], C-reactive protein [CRP]) were collected at start of induction, weekly for three weeks, and post-induction and were compared over time using paired t-tests. GA was administered at baseline and post-induction, and correlated with biomarker levels using Spearman correlations. Survival was estimated using Kaplan-Meier and compared by categorized biomarker level using Wilcoxon tests.ResultsBiomarker levels were stable during induction, except for CRP and IL-6 sR. Declines in objectively measured physical function [Short Physical Performance Battery (SPPB); r = 0.71, p < 0.01] and increases in self-reported limitation in instrumental activities of daily living (r = 0.81, p < 0.01) were correlated with increased TNFα sR1. Declines in SPPB were correlated with increased CRP (r = -0.73, p < 0.01). Improvement in depression was correlated with increased IL-6 sR (r = -0.59 p = 0.02). Survival was shorter in those with baseline TNFα or CRP levels above the median (6.1 vs. 40.2 months and 5.5 vs. 27.6 months respectively, p = 0.04 for both).ConclusionAmong older adults with AML, the relationships between TNFα sR1, CRP, and IL-6 sR with change in physical and emotional health during treatment warrants further investigation.
| S-EPMC6778500 | biostudies-literature
Project description: Not available
| S-EPMC10670451 | biostudies-literature
Project description:Acute myeloid leukemia (AML) most commonly affects patients older than 60 years. Outcomes of treatment of older AML patients have been poor. The advent of reduced-intensity conditioning (RIC) regimens made allogeneic hematopoietic cell transplantation (HCT) an available treatment option with curative intent for older AML patients. Because older patients are often excluded from clinical trials, little is known about the stratification of their risks before allogeneic HCT. While recent studies of RIC and allogeneic HCT have shown little impact of age on outcomes, other variables such as the recipient health status and the AML disease status and chromosomal aberrations have proven to be of prognostic significance. Here, the authors review recent studies of allogeneic HCT for older patients with AML with detailed evaluation of risk factors for relapse as well as non-relapse mortality. The authors have integrated the currently available information on transplant risks into a five-category risk-benefit system that could aid in the decision-making in this patient population.
| S-EPMC3875225 | biostudies-literature
Project description:Background and objectivesNovel, 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.Materials and methodsParticipants 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.ResultsNineteen 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.ConclusionLenalidomide 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.
| S-EPMC9326773 | biostudies-literature
Project description:Although clonal hematopoiesis (CH) can precede the development of acute myeloid leukemia (AML), it can also persist after achieving remission. Long-term clonal dynamics and clinical implications of persistent CH are not well understood. Here, we studied the prevalence, dynamics, and clinical implications of postremission CH in 164 AML patients who attained complete remission after induction chemotherapies. Postremission CH was identified in 79 (48%) patients. Postremission CH persisted long term in 91% of the trackable patients despite treatment with various types of consolidation and maintenance therapies. Postremission CH was eradicated in 20 out of 21 (95%) patients who underwent allogeneic stem cell transplant. Although patients with postremission CH as a group had comparable hematopoiesis with those without it, patients with persistent TET2 mutations showed significant neutropenia long term. Postremission CH had little impact on relapse risk, nonrelapse mortality, and incidence of atherosclerotic cardiovascular disease, although the clinical impact of post-CR CH was heterogeneous among different mutations. These data suggest that although residual clonal hematopoietic stem cells are generally resistant to consolidation and maintenance therapies, they retain the ability to maintain normal hematopoiesis and have little impact on clinical outcomes. Larger study is needed to dissect the gene-specific heterogeneity.
| S-EPMC8569418 | biostudies-literature
Project description:Purpose of reviewWe summarize recent advances for acute myeloid leukemia (AML) in older patients, with a focus on immunotherapeutics. Although the recently updated US SEER data still show that the majority of older AML patients do not receive any therapy, this reality is slowly changing. Advances in our understanding of the biology of AML and in the field of immunology are facilitating the development of alternative therapeutic options for patients, affording more and novel opportunities for potentially curative treatment.Recent findingsData from multiple cooperative groups show that older patients benefit from the incorporation of gemtuzumab ozogamicin, an anti-CD33 mAb toxin, into induction regimens. The first prospective study for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in older AML patients was reported at the American Society of Hematology Annual Meeting, 2012; the approach was feasible and improved disease-free survival over conventional chemotherapy. Proof-of-concept trials targeting specific antigens such as WT1 or novel unique leukemia-associated antigens are currently underway, as well as other trials using chimeric antigen receptor T cells or (natural killer/effector cells in nontransplantation settings.SummaryWider application of immunotherapies such as allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning have altered the landscape and offer potential for cure of an increasing number of older AML patients.
| S-EPMC4083702 | biostudies-literature