Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Abstract

Background: Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies.

Design and methods: To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade(®) (EPIC) study using International Working Group 2006 criteria.

Results: Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.

Conclusions: This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.

Figure 1.

Inclusion criteria and definitions of hematologic responses. Hb: hemoglobin; RBC: red blood cell.

Figure 2.

(A) Percentage of patients experiencing hematologic responses, (B) median time to hematologic responses during deferasirox treatment and (C) time from response onset to relapse in patients with hemoglobin, platelet and neutrophil hematologic responses. Trans, transfusion reduction-only response; Hb, hemoglobin improvement-only response; Hb+Trans, both transfusion reduction and hemoglobin response. On the neutrophil curve, from day 248, there is only one patient left at risk, leading to a drop on day 252 when he relapsed.

Figure 3.

Median decrease in serum ferritin from (A) baseline to end of study and over the course of the study in (B) erythroid, (C) platelet and (D) neutrophil analysis groups.