TY - JOUR
T1 - Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1-Risk Myelodysplastic Syndromes
T2 - A Randomized Trial
AU - Angelucci, Emanuele
AU - Li, Junmin
AU - Greenberg, Peter
AU - Wu, Depei
AU - Hou, Ming
AU - Montano Figueroa, Efreen Horacio
AU - Rodriguez, Maria Guadalupe
AU - Dong, Xunwei
AU - Ghosh, Jagannath
AU - Izquierdo, Miguel
AU - Garcia-Manero, Guillermo
AU - TELESTO Study Investigators
A2 - Grønbæk, Kirsten
PY - 2020/4/21
Y1 - 2020/4/21
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Blood Transfusion
KW - Cause of Death
KW - Deferasirox/adverse effects
KW - Double-Blind Method
KW - Female
KW - Ferritins/blood
KW - Humans
KW - Iron Chelating Agents/adverse effects
KW - Iron Overload/drug therapy
KW - Male
KW - Middle Aged
KW - Myelodysplastic Syndromes/complications
KW - Patient Acuity
KW - Progression-Free Survival
KW - Transfusion Reaction
KW - Young Adult
U2 - 10.7326/M19-0916
DO - 10.7326/M19-0916
M3 - Journal article
C2 - 32203980
SN - 0003-4819
VL - 172
SP - 513
EP - 522
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 8
ER -