Wide variability and inconsistency in reporting of results of Myelodysplastic Syndromes/neoplasms (MDS) clinical trials: An icMDS systematic review of published manuscripts
Abstract
Abstract Introduction: Standardized reporting of clinical trials results for MDS is essential to improve clinical interpretation and cross-study comparison. However, reporting of patient characteristics, response criteria, and endpoints in publications is often inconsistent; there is no systemic analysis of MDS trial reporting available. We conducted a systematic review of published MDS trial manuscripts on behalf of the international consortium for MDS (icMDS) to assess variability in reporting practices. Methods We searched ClinicalTrials.gov to identify all clinical trials registered for adults (≥18 years) with MDS that reported results between 2015-2024. Clinical trials that included acute myeloid leukemia (AML) or MDS/myeloproliferative neoplasms (MPN) were included if they enrolled ≥5 MDS patients. We excluded trials without an MDS cohort; non-therapeutic trials; trials focused on transplant interventions; or those which enrolled solid malignancies or other hematologic malignancies (chronic myeloid leukemia or lymphoid diseases). Finally, trials were required to have a manuscript available on Larvol, PubMed, or Google Scholar. Trials were categorized by disease risk (lower-risk [LR] vs. higher-risk [HR]) and trial phase (early phase [EP] vs. late phase [LP]). Results We identified 502 MDS trials on ClinicalTrials.gov, of which 351 did not meet inclusion criteria and 79 lacked a manuscript. A total of 72 trials (32 EP, 40 LP) with 80 publications (34 EP, 46 LP) were analyzed. Frequently reported baseline characteristics included age (100% EP, 100% LP), disease risk (74% EP, 74% LP), Eastern Cooperative Oncology Group performance status (85% EP, 72% LP), prior treatments (71% EP, 67% LP), and RBC transfusion dependency (32% EP, 70% LP). Less frequently reported characteristics included blood counts (hemoglobin [Hb; 38% EP, 54% LP], platelet count [38% EP, 54% LP], neutrophil count [24% EP and LP]) and bone marrow blasts (29% EP, 43% LP). Although disease risk was widely reported, definitions varied: IPSS and IPSS-R were each reported in 54% of manuscripts, while IPSS-M appeared in only 3%. Cytogenetic risk was separately reported in 39% of manuscripts (38% EP, 39% LP), and mutational data in 45% (47% EP, 43% LP). Responses per IWG 2006 criteria were reported in 84% of manuscripts. The primary endpoint involved safety/tolerability in 85% of EP manuscripts, though definitions were variable; recommended phase 2 dose was the most common (26% of EP manuscripts). In LP trials, primary endpoints were risk-specific: transfusion independence (TI) in 77% of LR, overall response rate (ORR) in 28% of HR, and complete remission (CR) or overall survival (OS) in 22% of HR. In HR manuscripts, CR was reported in 100%, ORR in 73%, hematologic improvement (HI) in 48%, RBC-TI in 23%, and OS in 80%. However, seven different definitions were used for ORR: CR + marrow CR + partial remission + HI per IWG 2006 was most common (35%). Event-free survival was reported in 25%; progression-free survival and relapse-free survival in 13%; and leukemia-free survival in 5%. Early mortality rate was reported in 35% (18% EP, 56% LP) and transplant rate in 58% (50% EP, 67% LP). Only 47% of HR and 90% of LR manuscripts identified HI-eligible patients. In LR-MDS, RBC-TI was reported in 72% of manuscripts but used six definitions. The most common were RBC-TI ≥8 weeks at any time during treatment (24%), ≥8 weeks within 28 weeks of treatment (13%), ≥8 weeks with Hb increase ≥1.0 (4%), ≥12 weeks with Hb increase ≥1.5 (4%), and ≥16 weeks within 24 weeks of treatment (12%). The remainder did not report RBC-TI, did not define it, or used a custom definition not used in another trial. HI was reported in 80% of LR papers with most of those reporting HI using IWG 2006 criteria (90%). Conclusion Reporting of baseline characteristics, response criteria, and outcomes is inconsistent in MDS clinical trials, with wide variability in response definitions, including ORR and TI. This heterogeneity limits interpretability, hampers historical comparisons and may obscure efficacy signals. Our findings highlight the need for standardized reporting guidelines to ensure clarity and consistency in MDS trial publications. As a next phase of this effort, we will conduct a formal Delphi process among icMDS experts to establish consensus recommendations for minimal and optimal MDS clinical trial reporting in manuscripts by disease risk (LR/HR) and trial phase (EP/LP).
Article Details
Authors (71)
Ted Getz
1Yale University and Yale Comprehensive Cancer Center, Department of Internal Medicine, Section of Medical Oncology and Hematology, New Haven, United States
Kelly Pugh
2The Ohio State University Comprehensive Cancer Center/James Cancer Hospital, The Ohio State University, Division of Hematology, Columbus, United States
Andrew Brunner
3Dana-Farber Cancer Institute, Boston, United States
Jan Philipp Bewersdorf
Amy DeZern
1Johns Hopkins University School of Medicine, Oncology, Baltimore, United States
Tariq Kewan
1Cleveland Clinic, Department of Translational Hematology and Oncology Research, Cleveland, United States
Uma Borate
2Ohio State University Comprehensive Cancer Center, Columbus, United States
Uwe Platzbecker
Mikkael Sekeres
13Sylvester Cancer Center, University of Miami Health System, Miami, United States
Andrew Wei
3Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Shahram Kordasti
Rena Buckstein
Gail Roboz
3Weill Cornell Medicine and The New York Presbyterian Hospital, New York, United States
Michael Savona
7Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, United States
Sanam Loghavi
Robert Hasserjian
13Massachusetts General Hospital, Department of Pathology, Boston, United States
Pierre Fenaux
David Sallman
Moffitt Cancer Cancer and Research Institute, Tampa, Florida, United States
Christopher Hourigan
13Fralin biomedical research institute, Virgina Tech University, Roanoke, United States
Matteo Della Porta
1IRCCS Humanitas Research Hospital, AI Center, Rozzano, Italy
Stephen Nimer
6Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Division of Hematology, Miami, United States
Richard Little
27National Cancer Institute, National Institutes of Health, Bethesda, United States
Valeria Santini
7DMSC University of Florence, AOUC, MDS Unit, Hematology, Florence, Italy
Fabio Efficace
1Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
Justin Taylor
Olatoyosi Odenike
University of Chicago Medicine and Comprehensive Cancer Center, Chicago
Tae Kon Kim
1Vanderbilt University Medical Center, Division of Hematology/Oncology, Department of Medicine, Nashville, United States
Stephanie Halene
Department of Pathology, Yale School of Medicine
Rami Komrokji
Moffitt Cancer Cancer and Research Institute, Tampa, Florida, United States
Elizabeth Griffiths
8Roswell Park Comprehensive Cancer Center, Buffalo, United States
Peter Greenberg
1Stanford University School of Medicine, Medicine, Stanford, United States
Mina Xu
1Yale School of Medicine, Hematology/Oncology, New Haven, United States
Zhuoer Xie
Moffitt Cancer Center, Tampa, Florida, United States
Rafael Bejar
Guillermo Sanz
26Hospital Universitario y Politécnico La Fe, Hematology Department, Valencia, Spain
Mrinal Patnaik
5Mayo Clinic, Rochester, United States
Maria E. Figueroa
6Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Division of Hematology, Miami, United States
Hetty Carraway
1Cleveland Clinic, Internal Medicine, Cleveland, United States
Omar Abdel-Wahab
Molecular Pharmacology Program, Sloan Kettering Institute
Daniel Starczynowski
3Cincinnati Children's Hospital Medical Center, Division of Experimental Hematology, Cincinnati, United States
Eric Padron
Moffitt Cancer Cancer and Research Institute, Tampa, Florida, United States
Jacqueline Boultwood
Steven Gore
Naval Daver
1The University of Texas MD Anderson Cancer Center, Houston, TX
Jane Churpek
2University of Wisconsin-Madison, Madison, United States
Ravi Majeti
1Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, United States
John Bennett
Department of Pathology
Alan List
7Halia Therapeutics, Inc., Lehi, Utah, United States
Adrian Mosquera Orgueira
36Instituto de Investigacións Sanitarias de Santiago, Complexo Hospitalario Universitario de Santiago de Compostela, Department of Hematology, Santiago de Compostela, Spain
Klaus Metzeler
4Department of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University of Leipzig, Leipzig, Germany
Francesc Sole
8Institut de Recerca Contra la Leucèmia Josep Carreras, Barcelona, Spain
Lisa Pleyer
Arjan van de Loosdrecht
12Amsterdam University, Amsterdam, Netherlands
Thomas Cluzeau
15Service d’Hématologie, Centre Hospitalier Universitaire de Nice, Nice, France
David Steensma
42Ajax Therapeutics, Cambridge, United States
Ghulam Mufti
43King's College, London, United Kingdom
Lionel Adès
Luca Lanino
3Yale University, New Haven, United States
Yazan Madanat
Anne Sophie Kubasch
16University Hospital of Leipzig, Department of Hematology, Dresden, Germany
Marie Sebert
1Hôpital Saint-Louis, Paris, France
R. Coleman Lindsley
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
Katharina S. Götze
Carmelo Gurnari
1Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH
Yasushi Miyazaki
3Atomic Bomb Disease Institute, Nagasaki University, Department of Haematology, Nagasaki, Japan
Aref Al-Kali
1Mayo Clinic, Division of Hematology, Department of Medicine, Rochester, United States
Abdulraheem Yacoub
7University of Kansas Medical Center, Westwood, United States
Bing Li
Ioannis Kotsianidis
29Department of Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
Maximilian Stahl
Amer Zeidan
18Yale School of Medicine - Yale Cancer Center, New Haven, United States