Emanuele Angelucci, MD; Junmin Li, MD; Peter Greenberg, MD; Depei Wu, MD; Ming Hou, MD; Efreen Horacio Montaňo Figueroa, MD; Maria Guadalupe Rodriguez, MD; Xunwei Dong, MD; Jagannath Ghosh, MS; Miguel Izquierdo, MD; Guillermo Garcia-Manero, MD; on behalf of the TELESTO Study Investigators *
Acknowledgment: The authors thank Rebecca Helson, PhD, Mudskipper Business Limited, for medical writing assistance and Sadhvi Khanna, Novartis Pharma SA, for statistical support.
Financial Support: By Novartis Pharma AG. Financial support for medical writing assistance was provided by Novartis Pharmaceuticals Corporation.
Disclosures: Dr. Angelucci reports personal fees from Novartis during the conduct of the study and personal fees from Novartis, Jazz Pharmaceuticals, bluebird bio, Roche, Celgene, Vertex Pharmaceuticals, and CRISPR Therapeutics outside the submitted work. Dr. Greenberg reports personal fees from Novartis during the conduct of the study and grants from H3 Biotech, Genentech, Notable Labs, and Celgene outside the submitted work. Dr. Izquierdo reports personal fees from Novartis during the conduct of the study. Dr. Garcia-Manero reports grants from Amphivena, Helsinn, Novartis, AbbVie, Celgene, Astex, Onconova, H3 Biomedicine, and Merck and consultancies for Amphivena, Celgene, and Astex outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-0916.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Data Sharing Statement: The following data will be made available with publication: deidentified participant data (trial data availability is in accordance with the criteria and process described on www.clinicalstudydatarequest.com). No other supporting documents to be made available (unless specifically requested). These data will be made available to qualified external researchers, for a specified purpose. Requests are reviewed and approved by an independent review panel on the basis of scientific merit (restrictions: Novartis is committed to sharing with qualified external researchers access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial, in line with applicable laws and regulations.).
Corresponding Author: Emanuele Angelucci, MD, Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy; e-mail, email@example.com.
Current Author Addresses: Dr. Angelucci: Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Dr Li: Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Dr. Greenberg: Stanford University Medical Center, 875 Blake Wilbur Drive, Room 2335, Stanford, CA 94305.
Dr. Wu: Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou 215006, China.
Dr. Hou: Department of Hematology, Qilu Hospital, Shandong University, No.107, Wenhua West Road, Ji'nan, China.
Dr. Montaňo Figueroa: Department of Hematology, Hospital General de México, Dr Balmis 148, 06720 Mexico City, Mexico.
Dr. Rodriguez: Department of Hematology, Hospital de Especialidades, Centro Médico Nacional La Raza, IMSS, Seris y Zaachila S/N, La Raza, Azcapotzalco, 02990 Mexico City, Mexico.
Dr. Dong and Mr. Ghosh: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936.
Dr. Izquierdo: Novartis Pharma AG, Novartis Campus, CH-4056 Basel, Switzerland.
Dr. Garcia-Manero: Section of Myelodysplastic Syndromes, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030.
Author Contributions: Conception and design: E. Angelucci, P. Greenberg, G. Garcia-Manero.
Analysis and interpretation of the data: E. Angelucci, P. Greenberg, X. Dong, J. Ghosh, M. Izquierdo, G. Garcia-Manero.
Drafting of the article: M. Izquierdo.
Critical revision of the article for important intellectual content: E. Angelucci, P. Greenberg, E.H. Montaňo Figueroa, M.G. Rodriguez, M. Izquierdo, G. Garcia-Manero.
Final approval of the article: E. Angelucci, J. Li, P. Greenberg, D. Wu, M. Hou, E.H. Montaňo Figueroa, M.G. Rodriguez, X. Dong, J. Ghosh, M. Izquierdo, G. Garcia-Manero.
Provision of study materials or patients: E. Angelucci, D. Wu, E.H. Montaňo Figueroa, M.G. Rodriguez, M. Izquierdo.
Administrative, technical, or logistic support: G. Garcia-Manero.
Collection and assembly of data: G. Garcia-Manero.
Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies.
To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1–risk MDS.
Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602)
60 centers in 16 countries.
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.
Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76).
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.
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.
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.
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.
Novartis Pharma AG.
Angelucci E, Li J, Greenberg P, et al, on behalf of the TELESTO Study Investigators. Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1–Risk Myelodysplastic Syndromes: A Randomized Trial. Ann Intern Med. 2020;:. [Epub ahead of print 24 March 2020]. doi: https://doi.org/10.7326/M19-0916
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Published: Ann Intern Med. 2020.
Published at www.annals.org on 24 March 2020
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