Wide variability and inconsistency in reporting of results of Myelodysplastic Syndromes/neoplasms (MDS) clinical trials: An icMDS systematic review of published manuscripts

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).

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Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-3852
Primary Topic
Acute Myeloid Leukemia Research
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article
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article

Wide variability and inconsistency in reporting of results of Myelodysplastic Syndromes/neoplasms (MDS) clinical trials: An icMDS systematic review of published manuscripts

Andrew H. Wei, Lionel Adès, Aref Al‐Kali, María E. Figueroa et al.
Blood
Acute Myeloid Leukemia Research
article

Wide variability and inconsistency in reporting of results of Myelodysplastic Syndromes/neoplasms (MDS) clinical trials: An icMDS systematic review of published manuscripts

Andrew H. Wei, Lionel Adès, Aref Al‐Kali, María E. Figueroa, Rami S. Komrokji, Gail J. Roboz, Uma Borate, Maximilian Stahl, Ιoannis Kotsianidis, Hetty E. Carraway, Jane E. Churpek, Stephen D. Nimer, Fabio Efficace, Omar Abdel‐Wahab, Klaus Hans Metzeler, Robert P. Hasserjian, David Andrew Sallman, Anne Sophie Kubasch, Naval Guastad Daver, Amy Elizabeth Dezern, Daniel T. Starczynowski, Tariq Zuheir Kewan, Peter L. Greenberg, Eric Padron, Jacqueline Boultwood, Rena J. Buckstein, Marie Sébert, Shahram Kordasti, Zhuoer Xie, Michael Robert Savona, Richard F. Little, Matteo Della Porta, Guillermo Sanz, Lisa Pleyer, Stephanie Halene, Mikkael Aaron Sekeres, Sanam Loghavi, Tae Kon Kim, Carmelo Gurnari, Olatoyosi M. Odenike, Elizabeth A. Griffiths, Christopher Simon Hourigan, John M. Bennett, Alan F. List, Katharina S. S. Götze, Amer Methqal Zeidan, Yasushi Miyazaki, Abdulraheem Yacoub, Mina L. Xu, Mrinal M. Patnaik, Ravindra Majeti, Uwe Platzbecker, Robert Coleman Lindsley, Thomas Cluzeau, Arjan van de Loosdrecht, Françesc Solé, Andrew M. Brunner, Jan Philipp Bewersdorf, Luca Lanino, Justin Taylor, Adrián Mosquera Orgueira, David P. Steensma, Yazan F. Madanat, Valeria Santini, Steven D. Gore, Pierre Fenaux, Rafael Bejar, Ghulam Mufti, Ted M. Getz, Kelly Pugh
article en

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).

BloodVol. 146(Supplement 1)
Cincinnati Children's Hospital Medical Center (US), Roswell Park Comprehensive Cancer Center (US), Cleveland Clinic (US), Sunnybrook Health Science Centre (CA), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), Humanitas University (IT), NewYork–Presbyterian Hospital (US), The University of Texas MD Anderson Cancer Center (US), King's College London (GB), Walter and Eliza Hall Institute of Medical Research (AU), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Medical University of Graz (AT), Université Paris Cité (FR), Cornell University (US), National Foundation for Cancer Research (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), Yale Cancer Center (US), University of Rochester Medical Center (US), Munich School of Philosophy (DE), Centre Hospitalier Universitaire de Nice (FR), Hospital Universitari i Politècnic La Fe (ES), Moffitt Cancer Center (US), University of Oxford (GB), University of Chicago (US), Massachusetts General Hospital (US), Josep Carreras Leukaemia Research Institute (ES), Complejo Hospitalario Universitario de Santiago (ES), Presbyterian Hospital (US), Assistance Publique – Hôpitaux de Paris (FR), The University of Kansas Cancer Center (US), Praxis BioSciences (United States) (US), University of Wisconsin Carbone Cancer Center (US), Azienda Ospedaliero-Universitaria Careggi (IT), Dana-Farber Cancer Institute (US), University Hospital Leipzig (DE), Leukemia Research Foundation (US), Health Economics and Outcomes Research (United Kingdom) (GB), National Cancer Institute (MY), Stanford Medicine (US), Biomedical Research Institute (US), National Cancer Institute (US), Hôpital Saint-Louis (FR), Oxford BioMedica (United Kingdom) (GB), Institute of Hematology & Blood Diseases Hospital (CN), Instituto de Investigación Sanitaria de Santiago (ES), Amsterdam University Medical Centers (NL), Io Therapeutics (United States) (US), King's College Hospital (GB), Sylvester Comprehensive Cancer Center (US), University Hospital of Alexandroupolis (GR), Sidney Kimmel Comprehensive Cancer Center (US), Nagasaki University Hospital (JP), The University of Texas Southwestern Medical Center (US), Vanderbilt University Medical Center (US), Stanford University (US)
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