ALBERT

Description: Abstract 3815 ESAs are recommended by the National Comprehensive Cancer Network for low-risk MDS patients with symptomatic anemia who have low serum erythropoietin (Epo) levels and limited transfusion burden. Because ESAs are costly and involve repeated physician office visits, socioeconomically vulnerable patients may be less likely to receive them. The advent of reporting MDS to the Surveillance Epidemiology and End Results (SEER) registries as a cancer beginning in 2001 affords the ability to examine population-based utilization of therapies for this group of disorders. Medicare patients diagnosed with MDS from 2001–2005 were identified in SEER registries. Medicare claims provided detailed treatment-related data on ESA use. Bivariate analyses and multivariate logistic regressions examined the effects of patient demographic, socioeconomic, geographic and health status characteristics, measured during 12 months prior to MDS diagnosis, on the probability of receiving ESAs between the year prior to SEER-reported diagnosis and either death or censoring. Analyses examined all MDS patients, and a subset with lower-risk MDS (modified French-American-British categories of refractory anemia (RA), RA with sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), or del(5q) syndrome). The MDS sample included 7,385 patients, with 2,568, or 35%, identified as lower-risk. 66% of MDS patients (70% of lower-risk) received ESAs at some point during the observation period. Multivariate estimates indicated that ESA use rates were higher among patients with an FAB classification of RARS relative to RA (Odds ratio [OR] 1.27; 95% Confidence interval [CI] 1.02–1.57), a history of transfusions prior to MDS diagnosis (OR 1.82; CI 1.58–2.09), diagnosis in 2004 versus 2001 (OR 1.21; CI 1.02–1.43), and residence in the South (OR 1.36; CI 1.12–1.65) or West (OR 1.28; CI 1.06–1.56) compared to the Northeast. Lower ESA use rates were also associated with baseline health status measures, including a diagnosis of dementia (OR 0.62; CI 0.51–0.76), other severe mental illness (OR 0.54; CI 0.36–0.83), use of a wheelchair (OR 0.71; CI 0.58–0.88) or nursing home stay (OR 0.40; CI 0.30–0.53), and demographic and socioeconomic characteristics including age 85+ compared to age 65–69 years (OR 0.76; CI 0.61–0.95), black versus white (OR 0.77; CI 0.62–0.97), prior-year enrollment in Medicaid or Medicare Savings Programs (MSP) (OR 0.63; CI 0.53–0.75), and area percent of adults without any college education (OR 0.99; CI 0.98–1.00, p

Description: Abstract 3178 Background: Anemia is present in up to 90% of patients (pts) with myelodysplastic syndromes (MDS), with as many as 40% developing red blood cell (RBC) transfusion-dependency. Though studies have reported clinical utility of iron chelation therapy (ICT) in MDS pts, its impact on overall survival from prospective studies is yet to be demonstrated. Reflective of this therapeutic equipoise and lack of uniform recommendations in the published guidelines, clinical utilization practices vary significantly. To better understand the utilization patterns of ICT, we conducted a retrospective analysis of a large transfusion-dependent MDS cohort enrolled in Medicare Part D from 2005 to 2008. Methods: MDS pts were identified using ICD-9 CM codes (1 inpatient or 2 outpatient) from a 100% Medicare sample. Pts meeting a minimum transfusion threshold of cumulative 20 packed RBC were considered “ICT eligible”. The study cohort consisted of ICT-eligible pts enrolled in Medicare Part D, allowing characterization of oral drug use. The observation period began the week (wk) after pts met the transfusion threshold and lasted until death or end of study. Transfusion use was captured based on specific Health Care Common Procedure Coding System (HCPCS) or revenue codes. Use of drugs, including ICT, was captured using specific HCPCS and National Drug Code (NDC) codes in Medicare Part B and D claims. Age at MDS diagnosis, race, and sex were determined from Medicare enrollment files. Logistic regression models were used to identify correlates of ICT use. Results: Among 125,290 MDS pts, 12,691 met the minimum transfusion threshold and were considered ICT eligible. Of those, 5,079 (40%) were enrolled in Medicare Part D and constituted the study cohort. In the study cohort, 65.6% of pts were ≥75 years old, 90% white, 47.8% males, and 13.9% had a poor predicted performance status (PS). MDS was classified as low-risk in 13.1%, 5q deletion-associated in 2.1%, high-risk in 6.9%, and not otherwise specified (NOS) in 77.9%. Common comorbidities included coronary artery disease (47.9%), congestive heart failure [CHF] (43.6%), cardiac conduction disorders or arrhythmias (44%), and renal disease (35.5%). The median follow-up was 95 wks (range 2–208). Pts were transfused a median of 13 (range 0–369) additional RBC units during the observation period. Among the entire study cohort, 793 patients (15.6%) received ICT; 513 (10.3%) received only deferasirox (DFX), 187 (3.8%) received only deferoxamine (DFO), and 93 (1.9%) received both. Median time from cohort entry to ICT initiation was 18 wks. The average dose for DFO was 2,932 mg/wk and for DFX, 1300 mg daily, relative to recommended levels of 10,000–14,000 mg/wk for DFO and 1,000–2,000 mg/daily for DFX. Median ICT therapy duration was 11 wks (1–168) for DFO, and 19 wks (1–139) for DFX. ICT was received for

Description: Abstract 3837 Background: Lenalidomide (LEN) was approved in the U.S. in December, 2005 for patients (pts) with transfusion-dependent (TD) anemia due to low- or intermediate-risk myelodysplastic syndromes (MDS) associated with a deletion 5q (del5q). In this patient population, Phase 2 clinical trial evidence indicates that 2/3 of TD pts achieved transfusion independence (TI), with 90% of pts achieving transfusion benefit by 3 months. This observational study examines LEN treatment patterns and association with reduced transfusion needs in a Medicare-enrolled population with MDS. Methods: MDS pts from 2006–8were identified using ICD-9 CM codes from 100% Medicare claims. Claims data from 2005–2008 were linked to Medicare enrollment files, and zip code-level measures of income and education from the 2000 U.S. Census. The study cohort consisted of MDS pts enrolled in Medicare Parts A and B and without Medicare Advantage (HMO enrollment) from 12 months before MDS diagnosis, and enrolled in Part D from diagnosis forward, allowing for observation of oral drug use. Patients were followed until death or end of study. LEN use was identified from Part D event files based on National Drug Code. Claims data were used to calculate duration, daily dose, time to initiation of treatment, and relationship to erythropoiesis-stimulating agents (ESAs) and hypomethylating agents (HMAs) use. Transfusion status was evaluated each week (wk), based on receipt of transfusions during the current and preceding 7-wk period (rolling). TD required transfusions during 2 of the 8 wks, separated by at least 3 wks. TI required a period of 8 wks without transfusions. An intermediate transfusion user (TU) category received 1 transfusion during the prior 8 wks. Change in transfusion status during a treatment episode was examined. Bivariate analyses examined sample means and proportions, overall and by MDS risk group defined based on initial diagnostic codes. Results: The cohort of 22,480 pts was predominantly white (88%) and female (58%), and 76% were age 75 years or older. MDS risk group was ICD-9 coded as 456 (2%) del5q, 5,989 (27%) other lower-risk, 1,277 (6%) higher-risk and 14,758 (75%) not otherwise specified (NOS). LEN use rates were 3% (n=716) overall, with 31% of del5q, 3% of other lower-risk, 5% of higher-risk and 2% of MDS NOS receiving therapy. Median time to initiate LEN (11.5 wks, range 0–132) was less for del5q (8 wks) than for other lower-risk coded patients (20 wks); most (86%) del5q pts and nearly all other lower-risk pts (96%) received ESAs prior to LEN. Pts received a mean of 4.1 4-wk cycles of LEN (median=2); 53% received

Description: Abstract 426 Background: While there is extensive evidence of the impact of iron chelation therapy (ICT) on clinical outcomes in thalassemia patients (pts), there is a paucity of data relevant to myelodysplastic syndromes (MDS). In this study, we examined the association between oral deferasirox (DFX) therapy and conditions potentially associated with iron overload [congestive heart failure (CHF) and endocrine disease (diabetes or thyroid)], drug side effects (renal disease), and overall mortality, among MDS pts in a U.S. Medicare cohort. Methods: MDS pts from 2005–2008 were identified using ICD-9 CM codes (1 inpatient or 2 outpatient) from the 100% Medicare claims database. Pts meeting a minimum transfusion threshold of 20 units packed RBC were considered “eligible” for ICT. The study cohort consisted of ICT-eligible pts enrolled in Medicare Part D, under which oral drug prescriptions are reimbursed. The observation period began the week (wk) after the RBC threshold was met and ended at incident diagnosis of a condition of interest, death, or end of study. Patients receiving parenteral ICT (deferoxamine) during the observation period were excluded. Patients with a history of the specific condition (CHF, endocrine disease, renal disease) were excluded from the outcome-specific sample, but were included in overall survival analysis. Onset of CHF or renal disease was based on the presence of 1 inpatient or 2 outpatient Medicare claims with ICD-9-CM diagnoses of each condition. Onset of diabetes or thyroid disease was measured based on new use of oral anti-diabetic or thyroid medications, respectively. Covariates in the outcome models included demographics (age, sex, race), ICD-9 coded MDS risk category at diagnosis, baseline indicators for co-morbid conditions, and time-varying exposure to RBC, erythropoiesis-stimulating agents (ESA), lenalidomide and hypomethylating agents (HMA). Marginal structural models (MSM) estimated the effects of cumulative DFX, controlling for anemia management and patient characteristics. The analysis adjusted for effects of time-varying health status on the probability of receiving DFX. Results: The cohort of 4,226 beneficiaries with MDS was 54% female, 90% white, with mean age of 77.7 years. MDS risk status was 16% lower/del5q, 5% higher, & 79% not otherwise specified. Common baseline comorbidities included CHF (46%), diabetes (18%), thyroid disease (21%), and renal disease (29%). Drug exposures prior to cohort entry included ESA (84%), HMA (19%) and lenalidomide (7%). Prior ICT was noted for 4.5% of patients. Patients were observed for a median of 35 weeks. Death occurred in 2496 (59%) of the cohort. DFX was used during the observation period by 544 (12%) patients, with mean duration of 29.2 weeks (median 20.5). Estimates from MSM indicate that each incremental week of DFX was associated with a decreased risk of death [hazard ratio (HR) 0.987; 95%CI 0.981–0.993]. The magnitude of risk reduction increased from HR 0.77 (95%CI 0.536–1.02) for patients receiving 14–26 weeks of DFX to HR 0.342 (95%CI 0.179–0.651) for patients with 53 or more weeks. Cumulative RBC units were associated with increased risk of death (HR 1.01, 95%CI 1.007–1.013 per unit), as were a baseline solid tumor diagnosis, renal and cardiac disease, and poor predicted performance status. After controlling for time-varying incidence of sepsis, bleeds, and cytopenias in MSM treatment propensity model, DFX use was not found to be associated with altered risk of CHF, endocrine or renal disease. Conclusions: This is the first large population-based Medicare study evaluating the association between DFX use in older MDS patients and sequelae of iron overload and mortality. The decrease in risk of death was proportional to the duration of therapy. Application of MSM addresses the role of observed time-varying confounders between treatment and outcomes, while permitting us to assess the duration-outcome relationships. The MSM analysis cannot address potential confounding by unobserved factors that may influence physician selection of patients for ICT. Nonetheless, this retrospective analysis controls for bias associated with observed patient health status, and lends significant support to a positive association of oral iron chelation therapy with decreased mortality in MDS patients with a minimum transfusion threshold, and ongoing transfusion needs. Disclosures: Gore: Celgene Corporation: Consultancy, Research Funding. Baer:Novartis, Inc.: Research Funding; Celgene, Inc.: Research Funding. Sasane:Novartis Pharmaceuticals: Employment. Paley:Novartis: Employment. Davidoff:GlaskoSmithKline: Research Funding; National Institutes of Health: Research Funding; Celgene: Research Funding; Novartis: Research Funding.