Clinical Outcomes Among Patients with Myelodysplastic Syndromes Treated with Iron Chelation Therapy: A Real World Medicare Database Study

Background: The majority of patients with myelodysplastic syndromes (MDS) develop anemia, and may require red blood cell (RBC) transfusions and become transfusion-dependent. Transfusion-dependency places patients at significant risk of developing iron overload. Iron chelation therapy (ICT) has been associated with improved overall and leukemia-free survival among MDS patients with iron overload. This study aims to assess the real-world treatment patterns of ICT among MDS patients, and its associated survival outcomes.

Methods: Using 100% Medicare claims data from 2006-2013, this retrospective cohort study included patients diagnosed with MDS, identified using ICD-9 codes (238.72-238.76). Selected patients entered the study cohort when they met a minimum transfusion threshold of either: 10 consecutive weeks with at least 1 unit of RBC transfusion, or 20 total units of RBC transfusions. Patients were classified into ICT and non-ICT cohorts depending on whether ICT was received after meeting the minimum transfusion threshold, and were observed until death or end of follow up in the database. Patient characteristics and clinical outcomes were compared between the ICT and non-ICT cohorts. Overall survival, acute myeloid leukemia (AML)-free survival, and cardiac event-free survival were assessed using Kaplan Meier (KM) survival analysis, as well as Cox regressions controlling for time-dependent ICT use and baseline characteristics. Survivals were estimated from time of cohort entry until the event.

Results: 591 (8.7%) of the 6,796 MDS patients who met the minimum transfusion threshold received ICT. Median weeks of ICT was 15.14 (range= 2.29 - 201.43 weeks). The ICT cohort was younger (77 vs. 80 years, P<0.01), had a higher proportion of males (58% vs. 52%, P<0.01), and had less comorbidity prior to cohort entry, compared with the non-ICT cohort. In KM survival analyses, the 1-year death rate was 66.5% in the non-ICT cohort compared with 27.6% in the ICT cohort (P<0.01). The 2-year death rate was 83.6% and 57.3%, respectively (P<0.01). The 1-year AML progression or death rate was 69.9% versus 34.3% (P<0.01), while the 1-year cardiac-event or death rate was 93.7% versus 78.9% (P<0.01), respectively. After controlling for baseline differences, ICT was associated with longer overall survival (Hazard Ratio [HR]= 0.85; 95% Confidence Interval [CI], 0.76 - 0.95), longer AML-free survival (HR=0.85; 95% CI, 0.76 - 0.94), and longer cardiac-event free survival (HR=0.85; 95% CI, 0.74 - 0.98), compared with the non-ICT cohort. Cox regression demonstrated that ICT initiation was significantly associated with being male (HR=1.30; 95% CI, 1.09 - 1.54) and lower comorbidities at cohort entry, including renal disease (HR=0.69; 95% CI, 0.58 - 0.83), gastrointestinal bleeding (HR=0.43; 95% CI, 0.32 - 0.58) and congestive heart failure (HR=0.81; 95% CI 0.68 - 0.97). Within the ICT cohort, almost all patients (583/591, 98.6%) received deferasirox as initial therapy.

Conclusions: The proportion of Medicare patients treated with ICT among MDS patients who met a minimum threshold of RBC transfusions was low in this study population. ICT among eligible MDS patients was associated with better overall, AML-free, and cardiac-event free survivals. It should be noted that the chelated group had fewer comorbidities, which may have contributed to the differences in clinical outcomes. Subsequent analyses are warranted, including the impact of duration of chelation.