Increase in Chemotherapy Use and Associated Survival Benefit Among Medicare-Aged Patients with Acute Myeloid Leukemia (AML)

Abstract Introduction: The incidence of AML increases with age and more than half of patients are diagnosed at age ≥ 65 years. The prognosis of patients aged ≥ 65 years is very poor and worsens with advancing age as treatment efficacy and tolerability have been shown to deteriorate markedly with age. The objective of this analysis was to examine treatment trends over time, factors predictive of therapy receipt and prognosis, and overall survival in an elderly AML population in routine clinical practice. Methods: This retrospective analysis utilized linked cancer registry claims data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 2000 to December 31, 2013, with Medicare enrollment and claims data through 2015, thus allowing a minimum 2-year follow-up. Patients were included if they were diagnosed with a first primary AML cancer, were aged > 66 years, and continuously enrolled in Medicare Parts A and B with no health maintenance organization (HMO) coverage in the year prior to diagnosis. Differences in patient characteristics by treatment status were assessed with the chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables. Unadjusted Kaplan-Meier survival curves with accompanying log-rank test were generated. A time-varying Cox proportional hazards regression model examined the relative risk of death by treatment status, adjusting for age, sex, race, prior myelodysplastic syndromes (MDS), poor performance indicators (PPIs), comorbidity burden, income, education, marital status, year of diagnosis, and geographic region. Results: Of the 11,142 patients analyzed in the study, 4,772 (43%) patients received treatment with chemotherapy within 3 months of diagnosis and 6,370 (57%) patients did not receive treatment. Treatment rates increased over the study time period from 36% in 2000 to 55% in 2013 (P < 0.0001; Figure 1). The mean age at diagnosis was 75 years for treated patients and 80 years for untreated patients (P < 0.0001). Forty-three percent of treated patients were over the age of 75 years at diagnosis compared with 74% of untreated patients. Treated patients were more likely to be male (54% vs 50%), be married (60% vs 46%), to have a lower incidence of prior MDS (14% vs 19%), were less likely to have PPIs (8% vs 19%), and had a lower comorbidity burden (54% vs 43% with a comorbidity score of 0) compared with untreated patients. The median unadjusted overall survival was 2.13 months for the overall population and was longer for treated patients (5.3 months) compared with untreated patients (1.6 months; log-rank P < 0.0001). In multivariate survival analysis, treated patients exhibited a 14% lower risk of death compared with untreated patients (hazard ratio 0.86; 95% CI 0.81-0.91). Patients receiving treatment within 30 days of diagnosis had a 67% reduction in 30-day mortality risk and a 41% reduction in 60-day mortality risk compared with those who did not receive treatment. Advanced age, higher comorbidity score, presence of PPIs, and being unmarried were significantly associated with higher mortality risk. Conclusions: Use of chemotherapy among the elderly AML patient population has increased over time. However, at the time of the analysis, about 45% of patients were still not receiving treatment, and the rate of undertreatment was even more pronounced among those aged > 75 years. The use of antileukemic therapy was associated with a significant survival benefit compared with palliative care, after controlling for age, comorbidities, poor performance, and other patient characteristics. An unmet treatment need among older AML patients persists. Disclosures Satram-Hoang: Genentech: Research Funding; Celgene Corp.: Research Funding. Parisi:Celgene Corp.: Employment, Equity Ownership.

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Comparative Effectiveness of Chemotherapy in an Elderly Acute Myeloid Leukemia Population in the United States

Blood ◽

10.1182/blood.v124.21.2272.2272 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2272-2272 ◽

Cited By ~ 1

Author(s):

Bruno C Medeiros ◽

Sacha Satram-Hoang ◽

Khang Q. Hoang ◽

Faiyaz Momin ◽

Deborah Hurst ◽

...

Keyword(s):

Overall Survival ◽

Elderly Patients ◽

Performance Indicators ◽

Survival Benefit ◽

Myeloid Leukemia ◽

Poor Performance ◽

Comorbidity Score ◽

Elderly Aml ◽

Comorbidity Burden ◽

Acute Myeloid

Abstract Introduction: A disproportionate number of newly diagnosed acute myeloid leukemia (AML) occurs in elderly patients. Conventional chemotherapy treatments for AML may be highly toxic and elderly patients often have increased comorbidity burden and loss of organ reserve that may impact their ability to tolerate therapy. Consequently, fewer than half of elderly patients with AML receive anti-leukemic therapy and outcomes among these patients have not improved in the last few decades. We described treatment patterns and outcomes of elderly AML patients in a real-world population. Methods: We utilized a retrospective cohort analysis of first primary AML patients in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 to December 31, 2009, >66 years, and continuously enrolled in Medicare Part A and B in the year prior to diagnosis. There were 8336 patients identified, of which 5009 (60%) did not receive treatment (NT). Chemotherapy agent definition was not possible in approximately 70% of patients who received therapy because chemotherapy was administered during inpatient stays which are paid based on ICD-9 diagnosis or procedures codes only and not chemotherapy codes. Of those initiating treatment within 3 months after diagnosis, 345 were treated with azacitidine + decitabine (AD) and 124 were treated with cytarabine+anthracycline (CA). Statistical comparisons were made between NT, AD and CA. To compare demographic and clinical characteristics by treatment, the Chi-square test for categorical variables and ANOVA or t-test for continuous variables was used. Kaplan-Meier curves and corresponding log-rank test were used to compare overall survival by treatment. Cox regression and propensity-weighted analyses estimated the relative risk of death adjusting for demographic and clinical factors. The date of last follow-up was December 31, 2010. Results: Patients receiving CA were younger (mean age 73 vs. 78 and 81), more likely male (62% vs. 59% and 50%), married (71% vs. 61% and 47%), had less secondary AML (7% vs. 21% and 19% with prior myelodysplastic syndrome [MDS]), less likely to have poor performance indicators (2% vs. 9% and 17%) and had lower comorbidity score compared to those receiving AD and NT, respectively. Similarities in age, comorbidity burden and proportion with high risk disease were noted in AD and NT patients. The median unadjusted overall survival was longer for patients treated with CA (18.9 months) compared to AD (6.6 months) and NT (1.7 months; log rank p <.0001). After adjusting for all covariates in the survival model, a 69% reduction in mortality was observed among patients treated with CA and a 53% reduction in mortality was observed among patients treated with AD, compared to those who did not receive any treatment (Table 1). The survival benefit of AD and CA were maintained in the younger (≤75) and older (>75) cohorts. Increasing age, increasing comorbidity score and presence of poor performance indicators were associated with significant increases in mortality. Propensity score adjusted multivariate analysis demonstrated similar risk reductions for CA (HR=0.41; 95% CI=0.34-0.49) and AD (HR=0.49; 95% CI=0.44-0.55). Conclusions: A substantial proportion of elderly AML patients are not receiving therapy for their disease. We observed a significant survival benefit with receiving treatment, even among the AD group who had similar characteristics to the NT group. Further, improved survival after receiving CA compared to AD was noted, but the propensity score adjusted analysis demonstrated similar reductions in death. The findings from this study can provide an important baseline for evaluating the benefits of new treatments under investigation. Table 1 Multivariate Overall Survival Analysis Covariates* n HR 95% CI Treatment Not Treated 5009 ref AD 345 0.47 0.42-0.53 CA 124 0.31 0.25-0.39 Age 66-70 537 ref 71-75 920 1.31 1.17-1.46 76-80 1276 1.42 1.27-1.58 >80 2745 1.68 1.52-1.86 Poor Performance Indicators No 4605 ref Yes 873 1.30 1.20-1.41 *Model also includes sex, race, comorbidity score, prior MDS, marital status, and geographic region Disclosures Satram-Hoang: Genentech, Inc.: Consultancy. Hurst:Genentech, Inc.: Employment. Reyes:Genentech, Inc.: Employment.

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The Relationship between Age and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in a Cohort of Older Patients with Acute Myeloid Leukemia (AML)

Blood ◽

10.1182/blood-2018-99-111274 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3588-3588

Author(s):

Bruno C. Medeiros ◽

Sacha Satram-Hoang ◽

Faiyaz Momin ◽

Monika Parisi

Keyword(s):

Overall Survival ◽

Mortality Risk ◽

Real World ◽

Survival Benefit ◽

Older Patients ◽

Research Funding ◽

Comorbidity Score ◽

Comorbidity Burden ◽

Medicare Database

Abstract Introduction: The use of allogeneic HSCT is considered a potential cure for AML but its use is limited in older patients because of significant comorbidities and increased transplant-related morbidity and mortality. However, there is evidence to suggest that older patients up to 80 years old may tolerate and benefit from intensive treatment, despite deteriorating organ function. This real-world analysis compared outcomes of Medicare-aged, chemotherapy-treated AML patients with or without HSCT. Methods: We performed a retrospective cohort analysis of 4,772 patients with a first primary AML in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 and December 31, 2013, were aged > 66 years, continuously enrolled in Medicare Part A and B with no health maintenance organization (HMO) coverage in the year prior to diagnosis, and had received chemotherapy treatment within 3 months of diagnosis. Demographic and clinical characteristics were compared between patients who received HSCT and those who did not, using chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables. Unadjusted Kaplan-Meier survival plots were used to assess overall survival. Cox proportional hazards regression modeling evaluated the independent effects of covariates on overall survival, including receipt of HSCT, age, sex, race, prior myelodysplastic syndromes (MDS), poor performance indicators (PPIs), comorbidity burden, income, education, marital status, year of diagnosis, and geographic region. Date of last follow-up was December 31, 2015, permitting a minimum 2-year follow-up. Results: Of 4,772 patients with a first primary AML in the linked SEER-Medicare database, 403 (8%) underwent HSCT therapy after chemotherapy and 4,369 (92%) did not. Rates of HSCT increased over the study time period from 7% in 2000 to 12% in 2012 (P = 0.0033). Of the 403 patients who underwent HSCT, the majority (82%) were aged ≤ 75 years. Overall, patients in the HSCT group were younger at diagnosis (71 vs 75 years), more likely to be male (63% vs 54%), be married (66% vs 60%), less likely to have high-risk disease (11% vs 15% with prior MDS) or PPIs (4% vs 8%), and had lower comorbidity burden (59% vs 53% with a comorbidity score of 0) versus patients treated with chemotherapy only. In a subset analysis stratified by age, the relationships observed between patient characteristics and HSCT receipt persisted in the younger cohort of patients (≤ 75 years) but not in the older cohort (> 75 years). The unadjusted median overall survival was higher for the HSCT group (14.2 months) versus the non-HSCT group (4.8 months; log-rank P < 0.0001). In multivariate survival analysis, patients who underwent HSCT had a 40% lower risk of death versus those who did not undergo HSCT (hazard ratio [HR] 0.60; 95% CI 0.53-0.67). Advanced age, male sex, higher comorbidity score, prior MDS, and PPIs were significantly associated with higher risk of mortality. Stratifying by age, the survival benefit with HSCT was only demonstrated in the younger cohort aged ≤ 75 years (HR 0.53; 95% CI 0.46-0.60); no difference in mortality risk was noted in the older cohort aged > 75 years (HR 0.85; 95% CI 0.67-1.08). Conclusions: Overall, only 8% of patients receiving antileukemic therapy underwent subsequent HSCT therapy, and 82% of patients who did undergo HSCT were aged ≤ 75 years. HSCT was associated with a 40% reduction in mortality risk versus patients receiving chemotherapy only, and the survival benefit was more pronounced among the younger cohort aged ≤ 75 years, with a 47% reduction in mortality risk. Chronologic age appears to be the driving factor in HSCT receipt and prognosis, and these findings provide important new information on real-world outcomes on the benefit of HSCT in an elderly population. Disclosures Satram-Hoang: Celgene Corp.: Research Funding; Genentech: Research Funding. Parisi:Celgene Corp.: Employment, Equity Ownership.

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Acute Declines in Renal Function during Intensive BP Lowering and Long-Term Risk of Death

Journal of the American Society of Nephrology ◽

10.1681/asn.2018040365 ◽

2018 ◽

Vol 29 (9) ◽

pp. 2401-2408 ◽

Cited By ~ 9

Author(s):

Elaine Ku ◽

Joachim H. Ix ◽

Kenneth Jamerson ◽

Navdeep Tangri ◽

Feng Lin ◽

...

Keyword(s):

Renal Function ◽

Mortality Risk ◽

Survival Benefit ◽

Reference Group ◽

American Study ◽

Mortality Benefit ◽

Cox Models ◽

Risk Of Death ◽

Egfr Decline

BackgroundDuring intensive BP lowering, acute declines in renal function are common, thought to be hemodynamic, and potentially reversible. We previously showed that acute declines in renal function ≥20% during intensive BP lowering were associated with higher risk of ESRD. Here, we determined whether acute declines in renal function during intensive BP lowering were associated with mortality risk among 1660 participants of the African American Study of Kidney Disease and Hypertension and the Modification of Diet in Renal Disease Trial.MethodsWe used Cox models to examine the association between percentage decline in eGFR (<5%, 5% to <20%, or ≥20%) between randomization and months 3–4 of the trials (period of therapy intensification) and death.ResultsIn adjusted analyses, compared with a <5% eGFR decline in the usual BP arm (reference), a 5% to <20% eGFR decline in the intensive BP arm was associated with a survival benefit (hazard ratio [HR], 0.77; 95% confidence interval [95% CI], 0.62 to 0.96), but a 5% to <20% eGFR decline in the usual BP arm was not (HR, 1.01; 95% CI, 0.81 to 1.26; P<0.05 for the interaction between intensive and usual BP arms for mortality risk). A ≥20% eGFR decline was not associated with risk of death in the intensive BP arm (HR, 1.18; 95% CI, 0.86 to 1.62), but it was associated with a higher risk of death in the usual BP arm (HR, 1.40; 95% CI, 1.04 to 1.89) compared with the reference group.ConclusionsIntensive BP lowering was associated with a mortality benefit only if declines in eGFR were <20%.

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Impact of Sex and Metabolic Comorbidities on COVID-19 Mortality Risk Across Age Groups: 66,646 Inpatients Across 613 U.S. Hospitals

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1787 ◽

2020 ◽

Author(s):

Katherine E Goodman ◽

Laurence S Magder ◽

Jonathan D Baghdadi ◽

Lisa Pineles ◽

Andrea R Levine ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Mortality Risk ◽

Age Groups ◽

Patient Characteristics ◽

Chronic Complications ◽

Risk Of Death ◽

Relative Risks ◽

Increased Risk ◽

Metabolic Comorbidities

Abstract Background The relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from COVID-19 remains incompletely understood. Emerging evidence suggests that metabolic risk factors may also vary by age. This study aimed to determine the association between common patient characteristics and mortality across age-groups among COVID-19 inpatients. Methods We performed a retrospective cohort study of patients discharged from hospitals in the Premier Healthcare Database between April – June 2020. Inpatients were identified using COVID-19 ICD-10-CM diagnosis codes. A priori-defined exposures were sex and present-on-admission hypertension, diabetes, obesity, and interactions between age and these comorbidities. Controlling for additional confounders, we evaluated relationships between these variables and in-hospital mortality in a log-binomial model. Results Among 66,646 (6.5%) admissions with a COVID-19 diagnosis, across 613 U.S. hospitals, 12,388 (18.6%) died in-hospital. In multivariable analysis, male sex was independently associated with 30% higher mortality risk (aRR, 1.30, 95% CI: 1.26 – 1.34). Diabetes without chronic complications was not a risk factor at any age (aRR 1.01, 95% CI: 0.96 – 1.06), and hypertension without chronic complications was only a risk factor in 20-39 year-olds (aRR, 1.68, 95% CI: 1.17 – 2.40). Diabetes with chronic complications, hypertension with chronic complications, and obesity were risk factors in most age-groups, with highest relative risks among 20-39 year-olds (respective aRRs 1.79, 2.33, 1.92; p-values ≤ 0.002). Conclusions Hospitalized men with COVID-19 are at increased risk of death across all ages. Hypertension, diabetes with chronic complications, and obesity demonstrated age-dependent effects, with the highest relative risks among adults aged 20-39.

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Big Data Analysis of Treatment Patterns and Outcomes Among Elderly Medicare Acute Myeloid Leukemia Patients

Blood ◽

10.1182/blood.v124.21.3698.3698 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3698-3698 ◽

Cited By ~ 1

Author(s):

Sacha Satram-Hoang ◽

Carolina Reyes ◽

Khang Q. Hoang ◽

Faiyaz Momin ◽

Deborah Hurst ◽

...

Keyword(s):

Overall Survival ◽

Performance Indicators ◽

Myeloid Leukemia ◽

Poor Performance ◽

Patient Characteristics ◽

Multivariate Survival Analysis ◽

Comorbidity Score ◽

Multivariate Survival ◽

Elderly Aml ◽

Acute Myeloid

Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute leukemia in adults with a median age at diagnosis of 66 years. Over half of the patients are diagnosed at age 65 or older and have shown no improvement in outcomes compared to younger patients in last few decades. The goal of the study was to examine the patient characteristics associated with receiving treatment and the survival outcomes in an older population in routine clinical practice. Methods: This retrospective cohort analysis utilized data from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The database is a nationally representative collection of Medicare patients in 18 population-based SEER cancer registries from diverse geographic areas representative of about 26% of the United States population. The analysis included 8336 first primary AML patients diagnosed between January 1, 2000 to December 31, 2009, >66 years, and continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis. Chi-square test for categorical variables and ANOVA or t-test for continuous variables was used to assess differences in patient and disease related characteristics by treatment status. Kaplan-Meier curves and Cox proportional hazards regression assessed survival by treatment status adjusting for age, sex, race, prior myelodysplastic syndrome (MDS), poor performance indicators (PPI), comorbidity, income, education, marital status, year of diagnosis and geographic region. Logistic regression modelling assessed patient characteristics predictive of not receiving treatment. Results: There were 3327 (40%) patients who received treatment with chemotherapy within 3 months of diagnosis and 5009 (60%) patients who did not receive treatment. Treatment rates increased over the study time-period from 35% in the year 2000 to 50% in 2009 (p<.0001). Treated patients were younger (75 vs. 81 years), more likely male (55% vs. 50%), married (61% vs. 47%), lower incidence of antecedent hematologic malignancy (15% vs. 19% prior MDS), less likely to have poor performance indicators (7% vs. 17%) and had lower comorbidity score (p<.0001) than untreated patients. In the treated cohort, 57%, 25%, 10% and 8% had NCI comorbidity score of 0, 1, 2, and ≥3 respectively. In the untreated cohort, 47%, 25%, 14% and 14% had NCI comorbidity score of 0, 1, 2, and ≥3 respectively. The most common comorbidities were hypertension (51%), hyperlipidemia (33%), coronary artery disease (25%), diabetes (21%), and atrial fibrillation (19%). In the logistic regression analysis, increasing age, increasing comorbidity score, black race, prior MDS and PPI were shown to significantly decrease the likelihood of receiving treatment. The median unadjusted overall survival was 2.5 months for the overall population and was longer for treated patients (6.1 months) compared to untreated patients (1.5 months; log rank p <.0001; Figure 1). In multivariate survival analysis, treated patients exhibited a 43% lower risk of death compared to untreated patients (HR=0.57; 95% CI=0.54-0.60). Increasing age, increasing comorbidity score and PPI were significantly associated with higher mortality risks. Conclusions: Although therapy use has increased over time, this large observational study showed that about 60% of elderly AML patients remain untreated following diagnosis. In the multivariate survival analysis, use of anti-leukemic therapy was associated with significant survival benefit in this cohort of patients. These results suggest an opportunity to improve treatment strategies and delivery to optimize patient outcomes in elderly AML patients. Figure 1: Unadjusted Overall Survival Figure 1:. Unadjusted Overall Survival Disclosures Satram-Hoang: Genentech, Inc.: Consultancy. Reyes:Genentech, Inc.: Employment. Hurst:Genentech, Inc.: Employment.

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118 Demographics and Real World Healthcare Cost and Utilization for Patients With Probable Tardive Dyskinesia

CNS Spectrums ◽

10.1017/s1092852918000160 ◽

2018 ◽

Vol 23 (1) ◽

pp. 75-75

Author(s):

Michael Polson ◽

Chuck Yonan ◽

Ted Williams

Keyword(s):

Tardive Dyskinesia ◽

Claims Data ◽

Prolonged Exposure ◽

Patient Characteristics ◽

Major Depressive ◽

Included Patient ◽

Comorbidity Burden ◽

History Of ◽

Study Population ◽

Funding Acknowledgements

AbstractBackgroundTardive dyskinesia (TD) is a movement disorder associated with prolonged exposure to antipsychotics. The current study was designed to describe demographics and comorbidities for patients with a dyskinesia diagnosis as probable TD (cohort 1), patients likely to have undiagnosed/uncoded TD (cohort 2), and a control population.MethodsThis retrospective study analyzed Medicaid claims data from July 2013-March 2017. For a pool of patients with a history of 3 months or more of taking an antipsychotic, three cohorts were evaluated: cohort 1 (ICD-9/10 codes for dyskinesia); cohort 2 (propensity score matching to cohort 1); and cohort 3 (patients withschizophrenia, major depressive disorder [MDD], and/or bipolar disorder [BD] and history of ≤2 antipsychotic medications). Outcomes included patient characteristics, Charlson Comorbity Index (CCI) and healthcare utilization (pre-and post [12-month] period).ResultsCohort sizes and characteristics were: cohort 1 (n=1,887; female, 68%; mean age, 42 years; MDD, 17%; BD, 48%); cohort 2 (n=1,572; female, 58%; mean age, 39 years; MDD, 22%; BD, 48%); cohort 3 (n=25,949; female, 67%; mean age, 40 years; MDD, 11%; BD, 49%). Cohorts 1 and 2 had higher comorbidity burden than cohort 3 (mean pre-index CCIs: 0.68, 0.79, and 0.47, respectively; p<0.001 for each cohort). After 12 months, mean per member per year healthcare costs were higher in cohort 1 and2 compared to cohort 3 ($21,293, $18,988, and $11,522, respectively), as were mean claims per member per year (185, 138, and 109, respectively).ConclusionIn the study population, patients likely suffering from TD, ICD-9/10 code-confirmed or unconfirmed, have a higher overall comorbidity burden and healthcareutilization than those who probably do not have TD.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.

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Which Patient Characteristics Impact Treatment Choice in Elderly Patients with Chronic Lymphocytic Leukemia?

Blood ◽

10.1182/blood.v120.21.967.967 ◽

2012 ◽

Vol 120 (21) ◽

pp. 967-967

Author(s):

Sacha Satram-Hoang ◽

Carolina Reyes ◽

Khang Hoang ◽

Faiyaz Momin ◽

Sridhar R Guduru ◽

...

Keyword(s):

Overall Survival ◽

Patient Characteristics ◽

Lymphocytic Leukemia ◽

Multivariate Survival Analysis ◽

Treatment Groups ◽

Risk Of Death ◽

Multivariate Survival ◽

Time Period ◽

Stage Disease ◽

Comorbidity Burden

Abstract Abstract 967 Introduction: Therapy selection in chronic lymphocytic leukemia (CLL) patients is based on the severity of the disease as well as patient characteristics such as age and comorbidity. National Comprehensive Cancer Network guidelines suggest that frail patients or those with significant comorbidity can be treated with oral chlorambucil (CLB) or single agent rituximab (R-mono). While treatment outcomes are mostly available from clinical trial data in younger patients, less is known about the effect of comorbidities on outcomes in elderly CLL patients in the real-world setting. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, was utilized in this retrospective cohort analysis of 3366 first primary CLL patients. Patients were diagnosed between January 1, 1998 to December 31, 2007, were >66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received first-line treatment with any oral or infused therapy. CLB is covered by Medicare Part D and data for its use were only available from 2007–2009 in the SEER-Medicare dataset. The NCI comorbidity index, a widely used and validated measure of comorbidity in cancer patients was assessed using claims in the year prior to diagnosis for each patient. Kaplan-Meier curves and Cox proportional hazards regression assessed survival by treatment type. Date of last follow-up was December 2009. Results: There were 153 CLB, 606 R-mono, 702 R+IV Chemo, and 1905 IV Chemo-only patients. CLB and R-mono patients were older at diagnosis with mean age of 77 compared to R+IV Chemo (73 years) and IV Chemo-only (76 years; p<.0001). 31% of R-mono patients were over the age of 80 at diagnosis (Table 1). CLB patients were more likely to be female and non-white compared to the other treatment groups (Table 1). R-mono patients had a higher comorbidity burden and were diagnosed with more advanced stage disease compared to other treatment groups (Table 1). R-mono patients also had a significantly higher amount of pre-existing anemia (95% vs. 77–88%; p<.0001) and thrombocytopenia (81% vs. 48–72%; p=0.0184) compared to other treatment groups. In the multivariate survival analysis we compared CLB to R-mono during the time period 2007–2009 and R+IV Chemo to IV Chemo-only during the time period 1998–2009. The unadjusted overall survival was higher for R-mono compared to CLB (log rank p=0.0478). The unadjusted overall survival was higher for R+IV Chemo compared to IV Chemo-only (log rank p <.0001) with 5-year overall survival rates of 72% (SE=1.09) versus 52% (SE=1.03) respectively. In multivariate survival analysis, adjusting for age, sex, race, stage, comorbidity, income, diagnosis year and geographic region, IV Chemo-only patients had a 39% higher risk of death compared to R+IV Chemo patients (HR=1.39; 95% CI=1.18-1.62) and CLB patients had a non-significant 2-fold higher risk of death compared to R-mono patients (HR=2.27; 95%CI=0.96-5.38). Increasing age and increasing comorbidity score were significantly associated with higher risks of mortality. Conclusions: Patient characteristics such as age, comorbidity burden and gender appear to be important factors in prescribing treatment for CLL. R-mono patients were the oldest with more advanced stage disease at diagnosis and highest comorbidity burden while R+IV Chemo patients were the youngest with earlier stage disease and lowest comorbidity burden. R-containing regimens exhibited a greater survival benefit compared to oral or infused chemo-only regimens. Disclosures: Satram-Hoang: Genentech, Inc.: Consultancy. Reyes:Genentech, Inc.: Employment, Roche Stock Other. Skettino:Genentech, Inc. : Employment, Roche Stock Other.

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Lenalidomide Treatment Is Not Related to AML Progression Risk but Is Associated with a Survival Benefit in RBC Transfusion-Dependent Patients with IPSS Low- or Int-1-Risk MDS with del5q: Results From a Comparative Study

Blood ◽

10.1182/blood.v118.21.119.119 ◽

2011 ◽

Vol 118 (21) ◽

pp. 119-119 ◽

Cited By ~ 1

Author(s):

Andrea Kuendgen ◽

Michael Lauseker ◽

Alan F. List ◽

Pierre Fenaux ◽

Aristoteles Giagounidis ◽

...

Keyword(s):

Lower Risk ◽

Survival Benefit ◽

Research Funding ◽

Employment Equity ◽

Factors Associated ◽

Risk Of Death ◽

Increased Risk ◽

Equity Ownership ◽

Rbc Transfusion ◽

Reduced Risk

Abstract Abstract 119 Background: Lenalidomide (LEN) treatment resulted in RBC transfusion independence for ≥ 8 wks in 51–67% of patients (pts) and cytogenetic response in 25–73% of pts with lower-risk MDS and del5q in 2 large multicenter trials (MDS-003 and -004) (List A et al. NEJM 2006;355:1456–65; Fenaux P et al. Blood 2011; doi:10.1182/blood-2011-01-330126). However, these studies were either single-arm or allowed early crossover to LEN, thus data on the influence of LEN on AML progression and overall survival (OS) is lacking. Aims: To assess the risk of AML progression and death in LEN-treated MDS-003 and -004 pts vs untreated MDS pts with del5q from a large multicenter registry, and to determine relevant risk factors. Methods: Data from 459 MDS pts with del5q entered into local or regional MDS registries were retrospectively collected from 9 centers (Europe, USA, Australia) using a uniform minimal data set. Eligible pt controls had IPSS Low-/Int-1-risk MDS and were RBC transfusion-dependent (≥ 1 unit/8 wks), reflecting the relevant inclusion criteria for both trials, and received best supportive care only including ESAs. Incidence of AML progression was assessed using a cumulative incidence estimator in the presence of competing risk (ie, death), and considering left truncation (LT) for the LEN cohort. OS was assessed using a cumulative probability estimator considering LT. Cox proportional hazards (PH) models with LT were used to assess the impact of LEN treatment and baseline factors (ie, age, sex, cytogenetics, bone marrow [BM] blast %, transfusion burden, no. of cytopenias, hemoglobin [Hgb] level [g/dL], and platelet and neutrophil counts) on risk of AML progression and death. LT is a statistical method to correct for different starting points of follow-up (ie, date of first LEN dose in clinical trial pts vs date of diagnosis in registry pts). Results: We analyzed 295 LEN-treated and 125 untreated pts. Baseline characteristics of treated (at first LEN dose) vs untreated (at diagnosis) pts were similar: mean age 65.0 vs 66.2 yrs; female sex 71% vs 68%; IPSS Low-/Int-1-risk 43%/57% vs 43%/57%. Median observation time was 4.3 vs 4.6 yrs. Baseline RBC transfusion burden was higher in the LEN cohort (median [range] units/8 wks: 6 [1–25] vs 2 [1–10]). Two- and 5-yr cumulative AML incidences were 7% and 23% for LEN vs 12% and 20% for the untreated cohort. Two- and 5-yr cumulative OS probabilities were 90% and 54% for LEN vs 74% and 41% for the untreated cohort. Median time to AML progression has not been reached for either cohort. Median OS was 5.2 yrs (95% CI 4.5–5.9) for LEN-treated vs 3.8 yrs (95% CI 2.9–4.8) for untreated pts. In the final Cox PH models, LEN treatment (hazard ratio [HR].939; p =.860) and 1 cytogenetic abnormality (abn) in addition to del5q (HR 1.111; p =.755) did not increase the risk of AML progression. Significant factors associated with an increased risk of AML progression were complex cytogenetics (del5q plus > 1 abn; HR 3.627; p =.002), BM blasts 5–10% (HR 2.215; p =.016), and higher transfusion burden (HR 1.097 [10% increase in risk per unit at baseline]; p =.029); higher Hgb levels were associated with a reduced risk (HR.857; p =.054). Regarding survival, LEN treatment was associated with a reduced risk of death (HR.597; p =.012). Other factors associated with decreased mortality were higher Hgb levels (HR.883; p =.028), higher platelet counts (HR.999; p =.035), and female sex (HR.598; p =.002). Higher transfusion burden (HR 1.056; p =.037) and age (HR 1.049; p <.001) increased the risk of death. In separate Cox PH models considering IPSS risk (Int-1 vs Low) and transfusion dependency for AML progression and OS, as well as age and sex for OS only, IPSS Int-1-risk was associated with an increased risk of AML progression (HR 1.689; p =.041) but not with an increased risk of death (HR 1.056; p =.723). Findings for LEN treatment when considering IPSS risk were similar to the final Cox PH models that considered individual covariates (AML progression: HR.892, p =.741; OS: HR.545; p =.003). Results were similar when Cox PH models were reanalyzed without LT. Conclusions: In this retrospective analysis of RBC transfusion-dependent pts with lower-risk MDS and del5q, LEN treatment was not associated with a higher risk of AML progression but led to a survival benefit vs untreated pts, despite a higher transfusion burden in the LEN cohort. Other significant risk factors for AML progression and death are consistent with previous findings in MDS pts. Disclosures: Kuendgen: Celgene Corporation: Honoraria. List:Celgene Corporation: Consultancy, Honoraria, Research Funding. Fenaux:Merck: Honoraria; Johnson & Johnson: Honoraria; Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Cephalon: Honoraria; Novartis: Honoraria. Giagounidis:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Brandenburg:Celgene Corporation: Employment, Equity Ownership. Backstrom:Celgene Corporation: Employment, Equity Ownership. Glasmacher:Celgene Corporation: Employment, Equity Ownership. Hasford:Celgene Corporation: Research Funding. Germing:Celgene Corporation: Honoraria, Research Funding.

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Effect of older age and comorbitities on outcomes with neoadjuvant chemotherapy (NAC) for epithelial ovarian cancer (EOC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17101 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17101-e17101

Author(s):

Zhaomin Xu ◽

Carla Francesca Justiniano ◽

Adan Z Becerra ◽

Christopher Thomas Aquina ◽

Francis P. Boscoe ◽

...

Keyword(s):

New York ◽

Survival Benefit ◽

Elderly Women ◽

New York State ◽

The Elderly ◽

Elderly Age ◽

Risk Of Death ◽

Comorbidity Burden ◽

The Impact

e17101 Background: Although a survival benefit for NAC has not been shown in the overall population of EOC, some patients may benefit from NAC. This analysis evaluates the role of age and comorbidities on the effect of NAC compared to upfront surgery on survival among EOC patients in New York. Methods: Patients who underwent surgery for stage II-IV EOC from 2006-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Elderly age was defined as >70 years. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Cox models were used to examine the effect of NAC on 5 year overall survival. The analysis was then stratified by age and comorbidity score to evaluate the role of NAC in specific subgroups. Results: 4617 patients met inclusion criteria of which 25% were elderly and 11% received NAC. Factors associated with receipt of NAC included age > 70, advanced stage, serous histology and high hospital volume (p<0.01). After adjustment for patient, hospital, and surgeon characteristics, NAC was associated with a 27% (p<0.01) increase in 5 year overall mortality in all EOC patients. Among the elderly, NAC did not have a significant effect on overall (p=0.47) or EOC-specific survival (p=0.24). Elderly and non-elderly women without comorbidities had a higher risk of death with NAC than primary surgery. There was a trend towards improved survival among elderly patients with higher comorbidity scores. (Table) Conclusions: The impact of NAC on EOC survival differs dependent on age and comorbidities. Patients with no comorbidities may have better prognosis with upfront surgery. Counterintuitively, those with more comorbidities, particularly the elderly, may derive survival benefit from upfront neoadjuvant therapy. [Table: see text]

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A Phase II Clinical Trial of Azacitidine and Vorinostat for Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) with Poor Performance Status, Comorbidities, Other Active Malignancies or Organ Dysfunction Not Eligible for Conventional Clinical Trials

Blood ◽

10.1182/blood.v128.22.1999.1999 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1999-1999 ◽

Cited By ~ 2

Author(s):

Guillermo Montalban-Bravo ◽

Xuelin Huang ◽

Elias J. Jabbour ◽

Gautam Borthakur ◽

Courtney D. DiNardo ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Organ Dysfunction ◽

Research Funding ◽

Performance Status ◽

Randomized Study ◽

Poor Performance ◽

Patient Characteristics ◽

Stopping Rules ◽

Poor Performance Status

Abstract INTRODUCTION: Most clinical trials exclude patients with poor performance, organ dysfunction, and presence of other active malignancies or comorbidities. Although some of these criteria are based on clinical reasoning, patients with such clinical features have dismal expected outcomes and limited therapeutic options and could therefore have a more favorable risk/benefit ratio if treated with a low intensity investigational intervention. The current study was designed to test whether it is feasible to treat patients not eligible for conventional studies in a clinical trial. METHODS: We conducted an initial Bayesian designed single-arm study and a subsequent randomized study for patients with AML or higher-risk MDS (intermediate-2 or high risk by IPSS) with either ECOG performance status (PS) ≥3, creatinine or bilirubin ≥2mg/dL, presence of other malignancy or other comorbidities. Primary endpoint was survival at day 60. The study included stopping rules for survival, response and toxicity. All patients received azacitidine 75mg/m2 sc daily for 5 days. Patients in the single-arm study and in the combination arm of the randomized study also received vorinostat 200mg tid for 5 days. Cycles could be repeated every 3-8 weeks. Responses were evaluated following the revised 2006 IWG criteria for patients with MDS and the IWG 2003 recommendations for patients with AML. Comorbidities were evaluated using the Adult Comorbidity Evaluation-27 (ACE-27) index. Adverse events (AEs) were assessed and graded according to the CTCAE v4 criteria. Overall survival (OS) was censored at the time of transplant. Event-free survival (EFS) was defined as the time interval between treatment start and date of resistance, progression or death. RESULTS: A total of 30 patients (16 with MDS, 14 with AML) were enrolled in the initial single-arm study. Patient characteristics and inclusion criteria are detailed in Table 1. Median age was 73 years (44-83). Median follow-up was 7.4 months (0.3-29). Sixty-day survival was 83%. Median number of cycles administered was 3.5 (1-12). The overall response rate (ORR) was 40% with 8 (27%) patients achieving CR, 4 with AML and 4 with MDS. Median OS was 7.8 months (0.3-29, CI 7.54-8.03) (Figure 1A) and median EFS was 5.1 months (0.3-15.9, CI 4.87-5.37) (Figure 1B). Stopping rules for survival and response were not met. Main adverse events (AEs) where grade 1-2 gastrointestinal toxicities. Mortality at 4 and 8 weeks was 10 and 20% respectively. A total of 79 patients were enrolled in the subsequent randomized study: 27 to azacitidine (A) and 52 to azacitidine and vorinostat (A+V). Patient characteristics and inclusion criteria are also shown in Table 1. Median age was 70 years (30-90). Forty-seven (59%) patients had MDS and 32 (41%) had AML. Median follow-up was 22.7 months (12.6-47.5). Sixty-day survival rates were 67% (A) and 85% (A+V), respectively (p=0.07). No differences in ORR (48% vs 46%, p=0.87), OS (6.1 vs 7.6 months, p=0.49) (Figure 1C) or EFS (3 vs 5.5 months, p=0.05) (Figure 1D) were observed between groups. Main AEs included grade 1-2 gastrointestinal toxicities with a higher proportion of AEs with A+V (81 vs 56%). Mortality at 4 and 8 weeks was 10% (A: 4, A+V: 4) and 19% (A: 9, A+V: 6) respectively. By univariate analysis neither PS ≥3, creatinine or bilirubin ≥2mg/dL nor presence of other malignancy were predictive for 60-day survival, OS or EFS. There were no significant differences in survival between patients with ACE-27 scores of 0-1 compared to 2-3 both in the single-arm (6.3 vs 7 months, HR=0.88, 95% CI 0.41-1.91, p=0.75) and the randomized phase of the study (A: 13.5m vs 6.1m, HR 0.93, 95% CI 0.27-3.17, p=0.9 and A+V: 12.1m vs 7.4m, HR 1.38, 95% CI 0.61-3.14, p=0.4). CONCLUSION: Most enrolled patients met the study's primary endpoint of survival at 60 days without major toxicity. Patients obtained clinical benefit with acceptable responses and survival despite their high comorbidity burden. Our results support the feasibility of treating patients with MDS or AML not eligible to other clinical trials due to poor performance status, comorbidities or organ dysfunction, with low intensity therapies within a clinical trial. These findings suggest relaxation of such criteria may likely increase the pool of clinical trial patient candidates and allow access to potential beneficial therapies for patients with otherwise dismal prognosis. Table 1 Table 1. Figure 1 Figure 1. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. DiNardo:Abbvie: Research Funding; Novartis: Research Funding; Agios: Research Funding; Daiichi Sankyo: Research Funding; Celgene: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Wierda:Genentech: Research Funding; Gilead: Research Funding; Novartis: Research Funding; Acerta: Research Funding; Abbvie: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Jain:Novimmune: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Abbvie: Research Funding; Infinity: Research Funding; Incyte: Research Funding; Seattle Genetics: Research Funding; BMS: Research Funding; Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria.

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