Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry

Abstract

Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.

Figure 1

Number of registry patients by transfusion and chelation status. *Cumulative red blood cell transfusion (RBCT) units >15 or RBCT intensity of >1 RBC unit/month or serum ferritin >1000 μg/L.

Figure 2

Overall survival by iron chelation therapy as a time-dependent variable in unmatched patients.

Figure 3

Overall survival by iron chelation therapy as a time-dependent variable in matched patients.

Figure 4

Adjusted overall survival by iron chelation therapy as a time-dependent variable in matched patients.

Figure 5

Changes in transfusion density over time in chelated and non-chelated patients. Time: eight 6-monthly visits.

Figure 6

Trajectory analysis in chelated patients with and without response and for non-chelated patients. (A) Monthly red blood cell transfusion density for chelated patients with and without an erythroid response and for non-chelated patients. (B) Ferritin levels of patients with and without a ferritin response, defined as a decrease of ≥1000 μg/L or a drop of the serum ferritin value below 1000 μg/L, and for non-chelated patients.

Figure 7

Serum creatinine levels (μmol/L) in chelated and non-chelated patients per check-up.