Utilization Patterns of Iron Chelation Therapy in Transfusion-Dependent Myelodysplastic Syndrome Patients Enrolled in Medicare Part D.

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.

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.

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 <26 wks in 60% of DFO and 57% of DFX users. Among ICT users, 71%, 37%, and 21%, received erythropoiesis-stimulating agents, hypomethylating agents (HMAs) and lenalidomide, respectively, during the observation period. No significant differences in ICT use were seen between low-risk, 5q deletion, and high-risk MDS pts (13.9% vs. 11.5% vs. 15.8%, P=0.52). In multivariate analysis using Cox proportional hazard models, the following were negatively associated with probability of receiving of ICT: age ≥ 90 years (Hazard ratio [HR] 0.557, 95%CI 0.347–0.894), female gender (HR 0.781, 95%CI 0.672–0.906), poor predicted PS (HR 0.725, 95%CI 0.541–0.972), history of CHF (HR 0.817, 95%CI 0.679–0.982), cardiac conduction disorders and arrhythmias (HR 0.824, 95%CI 0.694–0.979), and renal disease (HR 0.758, 95%CI 0.632–0.910). The likelihood of receiving ICT was higher among African American pts relative to whites (HR 1.579, 95%CI 1.157–2.156), residents of the South 2000 Census region (HR 1.27, 95%CI 1.005–1.604), and those pts receiving HMAs (HR 1.026, 95%CI 1.018–1.033) or lenalidomide (HR 1.007, 95%CI 1.003–1.012).

Overall, ICT utilization rates among elderly transfusion-dependent MDS pts and among those with significant comorbidities were low. Also, ICT therapy was more likely to be of short duration among the elderly. Utilization rates were higher for DFX than DFO, and doses closer to recommended levels for DFX than DFO, likely reflecting greater ease of administration.

Baer:Novartis, Inc.: Research Funding; Celgene, Inc.: Research Funding. Gore:Celgene Corporation: Consultancy, Research Funding. Sasane:Novartis Pharmaceuticals: Employment. Paley:Novartis: Employment. Davidoff:Celgene: Equity Ownership, Research Funding; National Institutes of Health: Research Funding; Novartis: Research Funding; GlaxoSmithKline: Research Funding.