Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1-Risk Myelodysplastic Syndromes: A Randomized Trial.

Background: Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies.

Objective: To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1-risk MDS.

Design: Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602).

Setting: 60 centers in 16 countries.

Participants: 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities.

Intervention: Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76).

Measurements: The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first.

Results: Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration.

Limitations: The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups.

Conclusion: The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients.

Primary Funding Source: Novartis Pharma AG.