Iron Chelation Therapy With Deferasirox Improves Survival Over Placebo in Lower-Risk MDS

In patients with lower-risk myelodysplastic syndromes (MDS) and iron overload (IO), treatment with iron chelation therapy (ICT) deferasirox was associated with longer event-free survival (EFS), fewer cardiac- and liver-related events, and fewer transformations to acute myeloid leukemia (AML) compared with placebo.

Further, the incidence of adverse events (AEs) associated with deferasirox was comparable to that observed in patients receiving placebo, according to Emanuele Angelucci, MD, from IRCCS Ospedale Policlinico in San Martino, Genova, Italy, who presented the results at the 2018 ASH Annual Meeting.

“Most patients with low- or intermediate-1–risk MDS [per the International Prognostic Scoring System criteria] eventually need chronic red blood cell transfusions because of impaired hematopoiesis, resulting in iron overload that damages organ function and contributes to shortened survival,” Dr. Angelucci explained during his presentation. While ICT has been proven effective in patients with lower-risk MDS, he noted, the studies are retrospective or registry studies – creating a need for data from prospective trials.

The randomized, double-blind, phase II TELESTO trial evaluated the safety and efficacy of deferasirox or placebo in 225 adults who were diagnosed with low/intermediate-1 risk MDS (confirmed by bone marrow examination) within the previous six months and had IO. Participants also were required to have a transfusion history of receiving between 15 and 75 packed red blood cell (pRBC) units, have a serum ferritin of >1000 ng/mL, and be free from cardiac, liver, and renal abnormalities.

Patients were excluded from the analysis if they had received six months of cumulative ICT (with either deferasirox or deferiprone) or if they had received transfusions for more than three years prior to enrollment.

The primary objective of the study, EFS, was assessed by a composite primary endpoint of time to first non-fatal event associated with cardiac and liver function and transformation to AML or death – whichever occurred first.

Following a 2:1 randomization protocol, patients received either deferasirox 10 to 40 mg/kg per day (n=149) or placebo (n=76).

Most patients in the cohort (72.4%) had intermediate-1-risk disease, and participants’ mean age was 61 years (range not reported). At six months before treatment assignment, patients in the deferasirox and placebo arms had received a similar number of pRBC transfusion units (20.28 and 20.27 units, respectively).

Participants in the deferasirox group experienced a significantly longer median EFS, compared with the placebo group: 1,440 days versus 1,091 days (hazard ratio [HR] = 0.64; 95% CI 0.42-0.96; p=0.01).

The three-year estimated rate of EFS also was greater with deferasirox (61.5% vs. 47.3%; p value not reported).

Median overall survival, however, was not significantly different between the deferasirox and placebo groups (1,907 days vs. 1,509 days; HR=0.83; 95% CI 0.54-1.28]; p=0.2).

The improvement in survival outcomes occurred without an increase in toxicity, Dr. Angelucci reported. The most common AEs in the deferasirox and placebo arms included:

  • worsening cardiac function (1.3% with deferasirox vs. 2.6% with placebo)
  • hospitalization for congestive heart failure (0.7% vs. 3.9%)
  • liver function impairment (0.7% vs. 1.3%)
  • progression to AML (6.7% vs. 7.9%)
  • death (32.2% vs 32.9%)

Diarrhea, pyrexia, upper respiratory tract infection, cough, and increased blood creatinine were reported in ≥20 percent of patients in either group. In addition, severe AEs (reported in ≥5% of patients) included anemia, pyrexia, thrombocytopenia, and lung infection. When the authors analyzed AE rates adjusting for differences in exposure times, the rate of all severe AEs were comparable in the deferasirox and placebo groups.

Noting one limitation of the trial, the authors said that possible differences in overall survival between the treatment groups may have been shrouded by the effects of ICT after discontinuation of study treatment.

The authors report financial relationships with Celgene, Vertex Pharmaceuticals, CRISPR CAS9 Therapeutics, Jazz Pharmaceuticals, Roche, and Novartis.


Angelucci E, Li J, Greenberg PL, et al. Safety and efficacy, including event-free survival, of deferasirox versus placebo in iron-overloaded patients with low- and int-1-risk myelodysplastic syndromes (MDS): outcomes from the randomized, double-blind Telesto study. Abstract #234. Presented at the 2018 ASH Annual Meeting, December 1, 2018; San Diego, CA.