Overall Survival In Older Patients Research Articles

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in older patients with metastatic cancer.

Treatment options for older patients with malignancies remain suboptimal. An accurate prognostic stratification could inform treatment decisions, which can potentially improve patient outcomes. Here, we sought to investigate whether the neutrophil-to-lymphocyte ratio (NLR) may have prognostic significance in patients with metastatic malignant tumors, with a special focus on older individuals. We retrospectively reviewed the clinical records of 3981 patients with histology-proven metastatic cancer who underwent radiotherapy between 2000 and 2013. The pretreatment NLR was determined within 7 days before treatment initiation. Patients aged ≥65 years were considered as older. We analyzed the prognostic significance of NLR for overall survival (OS) across all age groups. Compared with their younger counterparts, older patients showed a higher NLR (P < 0.001) and a lower OS (P < 0.001). Multivariate analysis revealed that a pretreatment NLR below the median was an independent favorable predictor of OS in both older (hazard ratio [HR]: 0.669, 95.0% CI: 0.605-0.740; P < 0.001) and younger patients (HR: 0.704; 95.0% CI: 0.648-0.765; P < 0.001). Regardless of age, patients who underwent systemic therapy showed more favorable OS, especially when NLR was low. In the older subgroup, the OS of patients with a low pretreatment NLR who did not undergo systemic therapy and of those with high pretreatment NLR who underwent systemic therapy was similar. A low pretreatment NLR predicts a more favorable OS in older patients with metastatic cancer. The most favorable OS was observed in patients with a low pretreatment NLR who received systemic therapy.

Impact of increased access to novel agents on the survival of multiple myeloma patients treated at a single New Zealand centre.

The impact of changes in novel agent (NA) usage on the survival of multiple myeloma (MM) patients in real-world hospital settings is unclear. In New Zealand (NZ) in 2011, frontline bortezomib became available and thalidomide availability was expanded. This retrospective study analyses the impact these change had on the survival of MM patients treated at a NZ hospital. Clinical and overall survival (OS) data were collected on MM patients who were treated at Christchurch Hospital during 2000-2009 (pre-cohort, n = 337) and 2011-2017 (post-cohort, n = 343). Outcomes were compared using pre-cohort data truncated at 2011. Patients in the post-cohort had significant increases (P < 0.001) in not only NA usage (85 vs 55%) and OS (median = 56 vs 44 months) but also the proportion (74 vs 49%) of young patients (age < 70) who received an autologous stem cell transplant (ASCT). Separate analysis of older patients demonstrated that those in the post-cohort had significantly longer OS (median OS 28 vs 17, P < 0.001) although 5-year relative survival remained less than 50%. Separate analysis of young patients demonstrated that those in the post-cohort had significantly increased initial OS with the survival curves converging at 5 years. Although ASCT-treated patients had similar OS in each cohort, their progression-free survival (PFS) was significantly increased in the post-cohort (median 40 vs 20 months, P < 0.0001). In the setting of a NZ hospital the increased availability of NA was associated with a significant improvement in both the OS of older patients and the PFS of ASCT patients.

MicroRNA-425 upregulation indicates better prognosis in younger acute myeloid leukemia patients undergoing chemotherapy.

The aim of the present study was to investigate whether the expression levels of microRNA-425 (miR-425) were associated with the prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 162 AML patients were enrolled and divided into chemotherapy and allo-HSCT groups. Next, the overall survival (OS) and event-free survival (EFS) were compared between patients with high and low miR-425 expression in each of the treatment groups. In the chemotherapy group, high miR-425 expression was favorable for EFS (P=0.001) and OS (P=0.001) in younger patients (<60 years), whereas it had no effect on EFS and OS in older patients (≥60 years). In the allo-HSCT group, there was no association between miR-425 expression levels and clinical outcomes. Further analyses suggested that in the low miR-425 expression group, EFS and OS were longer in patients treated with allo-HSCT as compared with those treated with chemotherapy (both P<0.001), whereas no significant differences were observed in the high miR-425 expression group. In conclusion, the current data indicated that miR-425 is an independent favorable prognostic factor for younger AML patients undergoing chemotherapy, and its use may facilitate clinical decision-making in selecting treatment for AML patients. Patients with low miR-425 expression may benefit from allo-HSCT, whereas allo-HSCT did not appear to be beneficial in patients with high miR-425 expression.

Impact of Hydroxyurea on Survival and Risk of Thrombosis Among Older Patients With Essential Thrombocythemia.

A retrospective cohort study was conducted of older adults (aged ≥66 years) diagnosed with ET from 2007 through 2013 using the linked SEER-Medicare database. Multivariable Cox proportional hazards regression models were used to assess the effect of HU on overall survival, and multivariable competing risk models were used to assess the effect of HU on the occurrence of thrombotic events. Of 1,010 patients, 745 (73.8%) received HU. Treatment with HU was associated with a significantly lower risk of death (hazard ratio [HR], 0.52; 95% CI, 0.43-0.64; P<.01). Every 10% increase in HU proportion of days covered was associated with a 12% decreased risk of death (HR, 0.88; 95% CI, 0.86-0.91; P<.01). Compared with nonusers, HU users also had a significantly lower risk of thrombotic events (HR, 0.51; 95% CI, 0.41-0.64; P<.01). Although underused in our study population, HU was associated with a reduced incidence of thrombotic events and improved overall survival in older patients with ET.

Overall survival in older patients with cancer

ObjectivesA growing number of patients with cancer are older adults. We sought to identify the predictors for overall survival (OS) in older adults with solid tumour and haematological malignancies between...

Upregulation of the EMT marker vimentin is associated with poor clinical outcome in acute myeloid leukemia

BackgroundVimentin (VIM) is a type III intermediate filament that maintains cell integrity, and is involved in cell migration, motility and adhesion. When overexpressed in solid cancers, vimentin drives epithelial to mesenchymal transition (EMT) and ultimately, metastasis. The effects of its overexpression in AML are unclear.MethodsIn this study, we analyzed the TCGA data of 173 AML patients for which complete clinical and expression data were available. In this analysis, we assessed the association between VIM mRNA expression and patient’s clinical and molecular characteristics including clinical outcome.ResultsVIM overexpression was associated with higher white blood count (< p = 0.0001). Patients with high VIM expression have worse overall survival (OS) and disease-free survival (DFS) compared with patients with low VIM expression (median OS; 7.95 months vs 19.2 months; p = 0.029). After age-stratification, high VIM expression was significantly associated with worse overall survival in older patients (age ≥ 60; median OS: 5.4 vs 9.9 months: p = 0.0257) but not in younger patients (age < 60). In stratification analysis according to cytogenetic status, high VIM expression was significantly associated with shorter OS (7.95 vs 24.6 months: p = 0.0102) in cytogenetically normal, but not in cytogenetic abnormal AML.ConclusionsCollectively, the data indicate that overexpression of the EMT marker vimentin is associated with poor clinical outcome in older patients with cytogenetically normal AML; and therefore may play a role in this disease.

Malnutrition and overall survival in older patients with cancer.

e22015Background: A growing number of patients with cancer are 65 years of age and older, and undergo age-related and cancer therapy-related changes. Malnutrition is common among cancer patients, a...

Socioeconomic and health system factors associated with lower utilization of hematopoietic cell transplantation in older patients with acute myeloid leukemia.

Receipt of hematopoietic cell transplantation (HCT) can improve overall survival in older patients with intermediate or high-risk acute myeloid leukemia (AML); however, utilization of HCT is poor. It is important to understand the factors that affect the receipt of HCT in a real-world setting among the older patients. We utilized the National Cancer Database to determine receipt of HCT in older patients (61-75 years) with intermediate or high-risk AML reported between 2003 and 2012. Multivariate logistic regression analysis was used to determine factors associated with receipt of HCT. Only 5.5% of older patients (n = 17,555) underwent HCT. Factors associated with a lower likelihood of receiving HCT included receipt of care in a non-academic hospital, race other than white, older age, Charlson comorbidity score of ≥1, uninsured status, Medicaid or Medicare insurance, and lower educational status. The receipt of HCT in older patients is low and varies based on biological as well as non-biologic factors, such as hospital type, insurance, and educational status. Nationwide efforts to improve access to HCT for appropriate patients are necessary.

Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer.

Identifying predictors of treatment toxicity and overall survival (OS) is important for selecting patients who will benefit from chemotherapy. In younger patients with cancer, muscle mass and radiodensity are associated with treatment toxicity and OS. In this study, we investigated whether muscle mass, radiodensity, and strength were associated with treatment toxicity and OS in patients with advanced cancer aged 60 years or older. Before starting palliative chemotherapy, muscle mass and radiodensity were assessed using computed tomography scans and muscle strength was assessed using a hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity resulting in dose reduction and/or discontinuation of treatment. Multiple logistic and Cox regression analyses were performed to study potential associations of muscle mass, radiodensity, and strength with treatment toxicity and OS, respectively. The participants were 103 patients, with a mean age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle parameters were not significantly associated with treatment toxicity. Higher muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence interval 1.00-1.05). Muscle mass and radiodensity were not significantly associated with OS. Higher muscle strength at the start of palliative chemotherapy is associated with significantly better OS in older patients with advanced cancer. None of the investigated muscle parameters were related to treatment toxicity. Future studies are needed to evaluate whether muscle strength can be used for treatment decisions in older patients with advanced cancer. This study in older patients with advanced cancer showed that adequate muscle strength is associated with longer overall survival. The results of this study imply that muscle strength might be helpful in estimating survival and therefore in identifying older patients who will benefit from anticancer treatment.

Use of frailty to predict survival in elderly patients with early stage non-small-cell lung cancer treated with stereotactic body radiation therapy.

Frailty has been shown to increase morbidity and mortality independent of age, but studies are lacking in radiation oncology. This study evaluates a modified frailty index (mFI) in predicting overall survival (OS) and non-cancer death for Stage I/II [N0M0] Non-Small-Cell Lung Cancer (NSCLC) patients treated with Stereotactic Body Radiation Therapy (SBRT). Medical records for all patients with Stage I/II NSCLC treated at our institution with SBRT from 2009 to 2014 were reviewed. A validated mFI score, consisting of 11 variables was calculated, classifying patients as non-frail (0-1) or frail (≥2). Primary endpoint (OS) was analyzed using Kaplan-Meier method and log-rank. Secondary endpoint, non-cancer death, was analyzed using Fine-Gray's method, with death from lung cancer as a competing risk. Patient cohort consisted of 38 (27.3%) non-frail and 101 (72.7%) frail [median total mFI score 3.0 (range 0-7)]. Median age and pack-year history was 74 and 46years, respectively. Median follow-up among survivors was 38.5months (range 4.0-74.1months). Frailty was associated with a lower 3-year OS (37.3% vs. 74.7%; p=0.003) and 3-year cumulative incidence of non-cancer death (36.7% vs. 12.5%; p=0.02). Frailty remained significant in the multivariate model [OS HR for mFI ≥2: 2.25 (1.14-4.44); p=0.02]. Frailty is associated with lower OS in older patients with early stage NSCLC treated with SBRT, yet frail patients survived a median 2.5years, and were more likely to die of causes unrelated to the primary lung cancer, suggesting SBRT should be considered even in older patients deemed unfit for surgery.

Hepatocellular carcinoma in elderly: Clinical characteristics, treatments and outcomes compared with younger adults.

The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The present study aims to evaluate the role of age on treatments and outcome of HCC patients. 1530 patients firstly diagnosed with HCC were retrospectively included and classified as older (≥65 years, n = 318, 21%) and younger patients (<65 years, n = 1212, 79%). The two groups were compared with clinical characteristics, tumor burden, Barcelona Clinics Liver Cancer (BCLC) stage, treatments and long-term prognosis. Elderly patients were more HCV infected, had more diabetes, poorer performance status, and were less aggressively treated. The proportion of HCC within BCLC stage 0-A, B or C was similar between the two groups, but elderly patients were more presented with BCLC stage D. The overall survival of older patients was poorer compared to younger patients before and after propensity score matching. However, elderly patients were less often effectively treated with surgery and loco-regional therapies across different BCLC stages. After stratified by BCLC stages or treatments, older patients showed comparable long-term outcome to younger patients. Performance status, BCLC stages and effective treatments, rather than age, was independent factors determining prognosis in the whole cohort and only elderly patients by multivariate analysis. In conclusion, older could have comparable survival to younger patients within the same tumor stage or after similar treatments. Thus, equally active treatments should be encouraged to elderly patients.

Neoadjuvant chemoradiation is associated with improved overall survival in older patients with esophageal cancer.

The aim of this study was to characterize outcomes associated with neoadjuvant chemoradiation prior to esophagectomy, compared to esophagectomy alone, in older patients with esophageal cancer. We conducted an observational cohort study in patients ≥70years with locally-advanced esophageal cancer undergoing esophagectomy ± neoadjuvant chemoradiation between 2006 and 2012 using the National Cancer Database. A Cox proportional hazards model with inverse probability of treatment weighting (IPTW) using the propensity score was developed to assess the association between trimodality therapy and overall survival. Perioperative complications and pathologic outcomes associated with trimodality therapy were identified with multivariable logistic regression. 1364 patients were included; the mean age was 75 (range 70-90). 904 (66%) were treated with trimodality therapy and 460 (34%) were treated with esophagectomy alone. On IPTW Cox analysis, neoadjuvant chemoradiation was associated with improved overall survival (HR=0.76, 95%CI [0.70-0.82], p≤0.001). Further, trimodality therapy was associated with lower rates of margin-positive resection (5% vs. 18%; OR=0.26, 95%CI [0.18-0.37], p<0.001) and in 18% of trimodality patients, there was no detectable tumor at surgery. 90-day mortality rates were not statistically different (14% vs. 12%; OR=0.99, 95%CI [0.73-1.36], p=0.22). Neoadjuvant chemoradiation was associated with lower 30-day readmission rates (5% vs. 8%; OR=0.48, 95%CI [0.31-0.73], p=0.004) and shorter surgical hospital stay (median 10 vs. 12days, p<0.001) compared to esophagectomy alone. In older patients with esophageal cancer, trimodality therapy, compared to esophagectomy alone, is associated with improved overall survival and favorable pathologic and perioperative outcomes. Further studies are needed to identify which older patients are most suitable for trimodality therapy.

Serum frailty biomarkers to predict overall survival in older patients with metastatic solid tumors: A substudy of prospective multi-center cohort study (KCSG PC13-09).

10041 Background: To determine individualized cancer treatment for older patients, easily measurable markers that predict functional decline and mortality are needed. The purpose of this study was to confirm prognostic value of potential biomarkers of frailty in older patients with metastatic solid tumors. Methods: Serum samples were prospectively collected before first line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors (KCSG PC13-09, WHO ICTRP number: KCT0001071). Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, Activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D (vitD) were measured by ELISA and IL-6, Myostatin, Irisin, FGF-19, FGF-21, FGF-23 by luminex mutiplex assay. Overall survival (OS) was studied by means of Kaplan-Meier, Log Rank and Cox methods. Results: Serum samples from 138 patients (median age: 75, range: 70-92) were collected from Feb 2014 to Dec 2016. During a median follow up time of 13.8 months, 72 (52.6%) patients had died. Among 13 serum markers, CRP (log-rank, P=0.006), Activin A (P=0.003), and Myostatin (P=0.043) were significantly correlated with OS in univariate analyses. In a Cox regression analysis, Activin A (HR 2.36, 95% CI 1.41-3.96; P=0.001) and Myostatin (HR 2.70, 95% CI 1.24-5.84; P=0.012) were significantly associated with OS after adjustment of other clinical factors (Age, Gender, ECOG PS, BMI, Geriatric assessment, Chemotherapy response, WBC, Albumin). Conclusions: In older cancer patients, high serum concentration of Activin A and Myostatin are predictive of poor OS. [Table: see text]

Phase I/II Study on Cytarabine and Idarubicin Combined with Escalating Doses of Clofarabine in Untreated Patients with Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10 CIARA)

Background: Clofarabine is a second-generation purine nucleoside analogue, which has shown synergistic activity with cytarabine. We determined the maximum tolerated dose (MTD, primary endpoint), safety and efficacy (secondary endpoints) of clofarabine in combination with cytarabine and idarubicin in newly diagnosed acute myeloid leukemia (AML) patients with high-risk for induction failure stratified in two age groups (< 60 years and ≥ 60 years).Methods: In this prospective, open-label, multicenter phase I/II study (EudraCT 2010-021719-18, CIARA trial), newly diagnosed AML patients with high risk of induction failure (NPM1 wildtype, FLT3-ITD negative), who were eligible for intensive chemotherapy, received two induction courses (cytarabine 750 mg/m2 d1-5, idarubicin 7.5 mg/m2 in patients <60 years or 6 mg/m2 in patients ≥60 years d1+3) with increasing doses of clofarabine (20-35 mg/m2 d1-5) following a 3+3 design with extension cohorts. Consolidation consisted of up to 3 courses of high-dose cytarabine or allogeneic hematopoietic cell transplantation (HCT).Results: Forty-two patients with de novo (n=32) or secondary (n=10) AML were included. Median age was 58.5 years (range 28-73, 24 patients < 60 years, 18 patients ≥ 60 years). Intermediate/adverse risk cytogenetics were found in 22 and 12 patients, respectively (karyotype missing in 8 patients). All patients received induction 1, 27 (64%) received induction 2; 4 (10%) patients died during induction courses 1 or 2. Eight patients developed a dose-limiting toxicity (6 patients with grade 3/4 non-hematologic toxicity and 3 patients with grade 4/5 hematologic toxicity) and the MTD was determined at 30 mg/m2 clofarabine for both age cohorts (younger patients: 2 of 6 patients with DLT at 35 mg/m2, no DLT at 30 mg/m2 (n=9); older patients: 4 of 6 patients with DLT at 35 mg/m2 in the extension phase, no DLT at 30 mg/m2 (n=3). The most frequent grade 3-5 non-hematologic adverse events were febrile neutropenia, sepsis, increased liver enzymes, pneumonia, decreased appetite and diarrhea occurring in 55, 24, 21, 21, 10 and 10% of patients. The median time to neutrophils ≥0.5/nl and platelets ≥50/nl after induction 1 was 25 and 24 days, respectively. Sixteen patients (38%) proceeded to allogeneic HCT in first CR and 8 (19%) received at least one course of high-dose cytarabine consolidation.Complete remission (CR) or CR with incomplete recovery (CRi) was achieved in 67%. After a median follow up of 2.2 years the 2-year overall survival (OS) was 56% and the 2-year event-free survival was 38% (median EFS 11.4 months). Compared to a matched historical control of 197 younger AML patients (SHG 0199 trial, Schlenk et al. NEJM 2008), the CR rate was 79% in the 24 younger CIARA patients compared to 66% in the control cohort (P=.18), and 2-year OS was higher for CIARA than for control patients (74% vs 49%, P=.021, Figure A). The allogeneic HCT rate in first CR (CR1) was higher in younger CIARA compared to younger control patients (58% vs 27%, P=.002). The CR rate in older CIARA patients was 50% compared to 36% in a historical control of 191 older patients, who were selected using the same genetic inclusion criteria as for CIARA patients (HD98B trial, Schlenk et al. Haematologica 2009, P=.23). Two-year OS in older patients was similar between CIARA and control patients (33% vs 17%, P=.31, Figure B). The allogeneic HCT rate in CR1 was 11% vs 2% in CIARA vs control patients (P=.029).Conclusion: Clofarabine can be safely administered at 30 mg/m2 in combination with cytarabine and idarubicin in younger and older newly diagnosed AML patients. Allogeneic HCT in CR1 was feasible in a high proportion of younger AML patients and likely contributed to the favorable outcome compared to historical control patients. [Display omitted] DisclosuresKrauter:Genzyme: Research Funding. Schlenk:Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Paschka:Novartis: Consultancy; Medupdate GmbH: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer Pharma GmbH: Honoraria; Celgene: Honoraria; ASTEX Pharmaceuticals: Consultancy. Lübbert:Ratiopharm: Other: Study drug valproic acid; Celgene: Other: Travel Funding; Janssen-Cilag: Other: Travel Funding, Research Funding. Janning:Teva: Honoraria. Becker:BMS: Honoraria; Novartis: Honoraria. Heuser:Tetralogic: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Honoraria; Pfizer: Research Funding; Bayer Pharma AG: Research Funding; BerGenBio: Research Funding; Karyopharm Therapeutics Inc: Research Funding.

Impact of Gene Mutations on Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine (AZA) or Conventional Care Regimens (CCR)

Impact of Gene Mutations on Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine (AZA) or Conventional Care Regimens (CCR)

Validity of the online PREDICT tool in older patients with breast cancer: a population-based study.

Background:Predicting breast cancer outcome in older patients is challenging, as it has been shown that the available tools are not accurate in older patients. The PREDICT tool may serve as an alternative tool, as it was developed in a cohort that included almost 1800 women aged 65 years or over. The aim of this study was to assess the validity of the online PREDICT tool in a population-based cohort of unselected older patients with breast cancer.Methods:Patients were included from the population-based FOCUS-cohort. Observed 5- and 10-year overall survival were estimated using the Kaplan–Meier method, and compared with predicted outcomes. Calibration was tested by composing calibration plots and Poisson Regression. Discriminatory accuracy was assessed by composing receiver-operator-curves and corresponding c-indices.Results:In all 2012 included patients, observed and predicted overall survival differed by 1.7%, 95% confidence interval (CI)=−0.3–3.7, for 5-year overall survival, and 4.5%, 95% CI=2.3–6.6, for 10-year overall survival. Poisson regression showed that 5-year overall survival did not significantly differ from the ideal line (standardised mortality ratio (SMR)=1.07, 95% CI=0.98–1.16, P=0.133), but 10-year overall survival was significantly different from the perfect calibration (SMR=1.12, 95% CI=1.05–1.20, P=0.0004). The c-index for 5-year overall survival was 0.73, 95% CI=0.70–0.75, and 0.74, 95% CI=0.72–0.76, for 10-year overall survival.Conclusions:PREDICT can accurately predict 5-year overall survival in older patients with breast cancer. Ten-year predicted overall survival was, however, slightly overestimated.

Epigenetic targeting approaches for acute myeloid leukemia: reports form the 56th American Society of Hematology annual meeting

Acute myeloid leukemia(AML)is a kind of genetic heterogeneous clonal hematopoietic stem cell disorder. Although there were improvements in the outcomes of selected younger patients and those with specific cytogenetic and molecular genetic characteristics, the overall survival for older patients remains dismal. In the last few years, next-generation sequencing technologies have identified recurrent mutations in genes encoding proteins involved in the epigenetic regulation of transcription in most patients with AML. This discovery has led to new insights into the role of the epigenome in AML and opens the possibility of epigenetically targeted therapies. This article will review the most important recurrent mutations in epigenetic regulatory genes and highlight the current and future treatment strategies that attempt to exploit epigenetic targets with the use of hypomethylating agents, which were reported on the 56th American Society of Hematology annual congress in 2014. Key words: Acute myeloid leukemia; Epigenetic, mutation; Hypomethylating agents; Targeting therapy; American Society of Hematology annual meeting

Overall Survival in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with >30% Bone Marrow Blasts Treated with Azacitidine By Cytogenetic Risk Status: Results of the AZA-AML-001 Study

Overall Survival in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with >30% Bone Marrow Blasts Treated with Azacitidine By Cytogenetic Risk Status: Results of the AZA-AML-001 Study

Comprehensive Geriatric Assessment Does Not Predict Overall Survival in Older Patients with Acute Myeloid Leukemia (AML)

BackgroundAge and cytogenetics are the strongest predictors of overall survival (OS) in older patients with acute myeloid leukemia (AML), but practitioners recognize that outcomes are also affected by medical comorbidities, physical function and a variety of psychosocial factors. Recent data suggest that geriatric assessment, including measures of physical, cognitive and psychological function, may be predictive of OS and helpful for risk stratification in AML (Klepin 2013). We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict overall survival in newly diagnosed older patients with AML.Patients and MethodsAll newly diagnosed AML patients age ≥60 years treated at Weill Cornell Medical Center and The New York Presbyterian Hospital completed a CGA including the OARS Physical Health Section, Mental Health Inventory (MHI-17), MOS Social Activity Survey, Activities of Daily Living (ADL) subscale of the MOS Physical Health, OARS Instrumental ADL subscale, Timed Up & Go, Blessed-Orientation-Memory-Concentration Test, and Karnofsky Performance Status (KPS). Laboratory data, medications, transfusions and days of hospitalization were also collected. Comorbidities were assessed using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI). OS was estimated by the Kaplan-Meier method and the log-rank test was used to compare survival profiles. The independent effects of the CGA and clinical risk factor variables on OS were estimated using hazard ratios in an adjusted Cox regression model.ResultsIn total, 126 patients were evaluated (median age 74, range 60-90). Fifty-one percent of patients had a HCT-CI score >1, with the most common comorbidities being a history of cancer (28.57%), cardiac disease (20.6%), and psychiatric disturbances (17.5%). Half of the patients had prior hematologic disorders and 29% had poor-risk cytogenetics. Most patients (84.9%) received decitabine-based induction strategies; 44 of these patients (34.9%) subsequently received intensive salvage regimens (median age 69). The other 19 patients (15.1%) were treated with standard induction chemotherapy, and 29 patients (21%) underwent allogeneic stem cell transplantation (median age 68). One hundred twenty-three patients (96.6%) completed the CGA with a mean time to completion of 26 minutes (± 8.9 minutes). Thirty-five percent of patients did not complete the entire assessment and only 61.1% completed the follow up CGA. Median OS was 11.1 months (range 0.36-52.64), with 1-year survival of 47.6%, complete remission (CR) rate of 39.8%, and 30-day mortality of 2.4%. In univariate analysis, age (P=0.0289), physician-assigned KPS (P=0.0031), sex (P=0.0074), ELN cytogenetic risk (P=0.0194), creatinine (P=0.027), albumin (P=0.0052), white blood cell (WBC) count (P=0.0135), LDH (P=0.0004), and treatment response (P=0.0001) were significant clinical predictors of OS. Significant CGA variables included Blessed Orientation-Memory-Concentration score (P=0.0035), Bend-Kneel-Stoop (P=0.0239), “someone to prepare your meals” (P=0.0253) and self-reporting of heart disease (P<0.001). In a multivariate analysis controlling for age and cytogenetic risk, physician-assigned KPS (HR, 1.804; 95% CI 1.175 to 2.768), self-reported cardiac history (HR, 2.290; 95% CI 1.383 to 3.794), and WBC count <11.2/ul (HR, 2.360; 95% CI 1.415 to 3.936) were the only independent prognostic factors for overall survival.ConclusionIn this study, age and cytogenetics remain the strongest predictors of OS in older patients with AML. While completion of the CGA was feasible, only performance status (KPS) was predictive of OS. Many measures previously reported as significant predictors of outcome, including impaired physical function (Klepin 2013), medication intake (Hurria 2011), pain (Sherman 2013), and HCT-CI score (Sorror 2005, 2009) were not predictive in our study population. The role of the CGA as a predictor of OS in AML requires further evaluation. The utility of the CGA in predicting functional performance and/or quality of life for older AML patients throughout treatment should also be investigated. DisclosuresRitchie:Celgene, Incyte: Speakers Bureau. Feldman:Ariad: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

The FLAG Chemotherapy Regimen Is an Alternative to Anthracycline Based Therapy for the Treatment of Acute Myeloid Leukemia for Patients with Multiple Co-Morbidities or Preexisting Cardiac Disease

BACKGROUND: Anthracycline based treatment for acute myeloid leukemia (AML) can be associated with significant morbidity and mortality amongst older patients or those with significant co-morbidities. Furthermore, for patients with previous anthracycline exposure or preexisting cardiac disease anthracyclines pose an increased risk of cardiotoxicity. For such patients intensive treatment options are limited.The FLAG (fludarabine, cytarabine and filgrastim) regimen is a non-anthracycline based chemotherapy useful for relapsed/refractory AML and as initial therapy for “fit” eligible patients. We present our experience using FLAG as first line therapy in a cohort of newly diagnosed AML patients with advanced age, significant co-morbidities or preexisting cardiac disease.METHODS: A single institution retrospective chart review was undertaken of patients treated with FLAG as frontline therapy from 2004 – 2013 with follow-up until June 2014. All patients were considered ineligible for standard '3+7’ treatment by the attending physician.RESULTS: Over the study period 56 patients received FLAG. Due to patient refusal or induction complications bone marrow assessments to ascertain remission status were not performed in 10 patients – to minimize bias these patients were evaluated for toxicity and overall survival (OS) but excluded from complete remission (CR) and relapse free survival (RFS) analysis.Of the 56 patients, 68% were males. The median age was 69 (21 – 80) with 79% aged ≥ 60 and 43% aged ≥ 70. Fifty-five percent (31) of the patients had primary AML and cytogenetics were favorable in 5% (3), intermediate in 66% (37), poor-risk in 21% (12) and failed in 7% (4). Forty-six percent (26) were treated with FLAG due to preexisting cardiac disease and others due to advanced age (20%), poor performance status (16%), co-morbidities (16%) or previous anthracycline exposure (2%). The ages of patients treated with FLAG due to cardiac disease or other reasons was similar (63.5 years vs. 66.9 years, p=0.27). Amongst patients with cardiac disease a pre-chemotherapy cardiac evaluation revealed wall motion abnormalities in 39% and an ejection fraction (EF) ranging from 33% - 81% with a borderline (≤ 50-51%) EF in 46%.Febrile neutropenia was observed in 82% (46) of patients, 27% (15) required intensive care support and the induction mortality was 16% (9). Amongst patients evaluated for a CR (46/56), 48% (22/46) obtained a CR. Although a CR was seen in 100% (3/3), 46% (15/33) and 37% (3/8) of patients with favorable, intermediate and poor-risk cytogenetics respectively there was no statistically significant difference (p=0.22) between groups. A CR was obtained in two additional patients following a second course of FLAG for an overall CR rate of 52% (24/46). Of these 24 patients, 8 (33.3%) received no additional treatment while 16 (66.7%) received consolidative chemotherapy. Of 10 eligible patients, 4 proceeded to an allogeneic stem cell transplant (allo-SCT) including two with preexisting cardiac disease.Of patients not transplanted 50% (10/20) eventually relapsed. There was no difference in relapse rates for those receiving FLAG for age/co-morbidities vs. cardiac disease (60% vs. 40%, p= 0.66) or for patients age <60 vs. ≥ 60 (50% vs. 50%, p=1.0). The median RFS was 441 days with no difference between patients treated with FLAG for cardiac reasons vs. other reasons (p=0.33) or for patient’s age < 60 vs. ≥ 60 (p=0.66).The median OS for the 56 patients was 278 days with 1 and 2 year survivals of 44% and 22% respectively. The median OS for patient’s age < 60 was higher than those age ≥ 60 (1102 days vs. 218 days, p=0.009) but there was no difference in the OS between patients treated with FLAG for cardiac disease and those treated for other reasons (305 days vs. 254 days, p=0.202). The median survival of patients with favorable, intermediate and unfavorable risk cytogenetics was 523 days, 311 days and 87 days respectively but this was not statistically significant (p=0.25) likely due to limited patient numbers.Conclusions: The FLAG regimen is a non-anthracycline based regimen that may serve as an alternative to the standard '3+7’ induction for AML in older adults or those with significant co-morbidities including preexisting cardiac disease. It is associated with comparable remission rates and overall survival in older patients. In addition, it may allow some patients with preexisting cardiac disease to proceed to allo-SCT. DisclosuresNo relevant conflicts of interest to declare.