24-Month Analysis of the Impact of Chelation on Clinical Outcomes in a 600 Patient Registry of Lower-Risk MDS Patients

Many patients with MDS require regular transfusions. Several reviews have documented poorer clinical outcomes and overall survival (OS) in transfusion-dependent MDS patients. A US registry of 600 lower-risk MDS patients prospectively collected data on clinical outcomes in chelated and non-chelated transfused patients. This 24-month interim analysis reports on cardiac events, leukemic transformation and OS.

This is a 5-year, non-interventional registry in MDS patients (aged ≥18 years) with lower-risk MDS (based on WHO, FAB and/or IPSS criteria) from 107 US centers. Patients had to have transfusional iron overload (serum ferritin ≥1000 μg/L and/or ≥20 packed red blood cell units and/or ongoing transfusion requirement of ≥6 units every 12 weeks). Follow-up was every 6 months for up to 60 months or death. Use of chelation therapy was not required. Chelated patients were those who had ever used iron chelation; a sub-analysis was done on patients with ≥6 months chelation. Assessments included demographics, disease status, MDS therapy, comorbidities, and causes of death. Differences between non-chelated and chelated patients are reported.

600 patients enrolled; as of May 26, 2011, 249 continued in the registry. 351 patients discontinued due to: lost to follow-up (n=51, 8.5%); death (n=278, 46.3%); other (n=22, 3.7%). 263/600 patients received chelation therapy, of whom 191 received ≥6 months.

Leukemic transformation and cardiac events were more common in non-chelated patients (Table 2). Time to leukemic transformation was significantly shorter in non-chelated versus chelated patients. A greater percentage of deaths occurred in non-chelated patients; time to death was significantly shorter in non-chelated versus chelated patients. The most frequent reasons for death were MDS/AML, cardiac, and infection.

At baseline, non-chelated patients had a higher incidence of cardiac disorders than chelated patients (51.3% vs 35%). While on the registry, non-chelated patients had a higher incidence of comorbidities than did chelated patients, predominantly vascular, cardiac and endocrine. Lifetime use of MDS therapies (pre- and on-registry) was lower among non-chelated versus chelated patients (88.4% vs 94.3%).

At the 24-month analysis, use of chelation was associated with lower AML transformation, fewer cardiac events, and better OS. The two patients groups had similar age, gender, and risk status breakdown (IPSS); however the non-chelated group had a higher prevalence of cardiac comorbidities. Ongoing follow-up for the 5-year duration of this registry will provide further data on differences in outcomes between chelated and non-chelated patients.

Lyons:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Telik: Research Funding; Alexion: Consultancy, Honoraria; Novartis: Research Funding. Sharma:Novartis: Employment. Paley:Novartis: Employment. Esposito:Novartis: Employment.