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First prospective evidence supporting iron chelation in patients with low and intermediate-1 risk myelodysplastic syndromes

The majority of patients with lower-risk myelodysplastic syndromes (MDS) eventually need chronic red blood cell (RBC) transfusions because of impaired hematopoiesis. Over time, the routine use of RBC transfusions results in iron overload which in turn can cause organ damage and contribute to a shorter survival. Several retrospective studies already suggested that iron chelation may improve outcomes in patients with lower-risk MDS, but this has never been validated in a prospective study. This has changed with the presentation of the phase II, randomized TELESTO trial during the 2018 annual meeting of the American Society of Hematology (ASH). In this study, deferasirox was shown to provide clinical benefit across multiple tissues, leading to a longer event-free survival (EFS) than what was seen with placebo. This includes a lower rate of cardiac and liver events and less transformations to AML.

Notwithstanding the fact that several retrospective and registry studies demonstrated improved outcomes with iron chelation in patients with lower-risk MDS, there was still considerable debate on the clinical utility of iron chelation in this patient population. To make an end to this debate, the TELESTO trial prospectively evaluated the EFS and safety of iron chelation therapy with deferasirox vs. placebo in patients with low/intermediate-1 risk MDS. TELESTO was initially designed as a phase III trial with a target enrollment of 630 patients, but the slow patient accrual forced investigators to reduce the target sample and change the study design into a phase II trial with a target enrollment of 210 patients. This new trial design makes it impossible to make statistical comparisons. In order to be eligible for the trial, patients had to be at least 18 years old and have IPSS low/intermediate-1-risk MDS (confirmed by a bone marrow (BM) examination within 6 months of study entry). Patients were required to have a serum ferritin (SF) level >1,000 ng/mL, have a transfusion history of 15–75 pRBC units and were not allowed to suffer from cardiac, liver or renal abnormalities. In total, 225 patients were randomized (2:1) to deferasirox (10–40 mg/kg/day based on dosing guidelines) or placebo.

Baseline patient and disease characteristics were well balanced between the two treatment arms, but more patients in the deferasirox arm were 75 years or older (25.5% vs. 17.1%). Patients in the deferasirox and placebo arm received a mean of 20.28 and 20.27 international units of pRBC transfusions 6 months prior to randomization. The median time on treatment was 217 days longer with deferasirox than with placebo (587.5 vs. 370.5 days). In total, respectively 43.9% and 25.0% of deferasirox and placebo patients received treatment for at least 2 years. The mean dose of deferasirox was lower than with placebo (14.9 mg/kg/day vs. 23.5 mg/kg/day), which reflects dose adjustment for SF level changes.

The median EFS was prolonged by 349 days with deferasirox (1,440 days; 95%CI: 1,167-1,559) compared to placebo (1,091 days; 95%CI: 820-1,348). This corresponds to a 36.4% risk reduction in EFS with deferasirox (HR[95%CI]: 0.636[0.42-0.96]; p=0.015). The estimated EFS rate at 3 years was reported at 61.5% with deferasirox as compared to 47.3% with placebo. Progression to AML as first event was seen in 6.7% of patients on deferasirox vs. 7.9% with placebo. Other events of interest with deferasirox vs. placebo included worsening of cardiac function (1.3% vs. 2.6%), hospitalization for congestive heart failure (0.7% vs. 3.9%); liver function impairment (0.7% vs. 1.3%) and death (32.2% vs. 32.9%).

The median overall survival (OS) was prolonged by 398 days with deferasirox vs. placebo (1,907 vs. 1,509 days; HR[95%CI]: 0.832[0.54-1.28], p=0.200). Of note, 52.1% of placebo patients started iron chelation therapy after study discontinuation, which may have diluted any potential OS difference. Finally, the levels of SF were found to decline over time with deferasirox while the level increased in the placebo arm.

After adjustment for exposure, the most frequently reported adverse events (AEs) with deferasirox vs. placebo were diarrhea (24.7% vs. 23.9%), pyrexia (21.8 vs. 18.7%), upper respiratory tract infection (16.7% vs. 22.7%), cough (12.6% vs. 11.3%) and an increased level of blood creatinine (15.9% vs. 0.9%). The incidence of fatigue (8.0% vs. 13.5%), constipation (7.0% vs. 12.9%), headache (6.3% vs. 14.6%) and abdominal pain (4.9% vs. 10.1%) was consistently lower with deferasirox than with placebo.

In conclusion, TELESTO is the first prospective, randomized study in patients with low/intermediate-1-risk MDS with iron overload demonstrating clinical benefit with iron chelation therapy across multiple tissues. This leads to a longer EFS, with lower rates of cardiac and liver events and less transformation to AML with deferasirox compared to placebo.



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. Presented at ASH 2018; Abstract 234.

Speaker Emanuele Angelucci


Emanuele Angelucci, MD, Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy


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