Representation of therapy-related myelodysplastic syndrome in clinical trials over the past 20 years.

Abstract

Therapy-related myelodysplastic syndrome (t-MDS), defined as MDS occurring after previous exposure to chemotherapy or radiotherapy, constitutes 10% to 20% of all MDS diagnoses. t-MDS patients tend to have higher-risk disease and worse outcomes than de novo MDS patients and are often excluded from therapeutic clinical trials. To explore this further, we extracted clinical trials across all status types registered on ClinicalTrials.gov from 1999 to 2018 studying untreated MDS patients. Using these specific search criteria, we analyzed 317 therapeutic MDS trials based on study status, therapeutic indication, eligibility criteria, and sponsor type to examine if these factors influenced t-MDS patient inclusion. Only 18 studies (5.7%) accrued 231 t-MDS patients in total, representing 3.2% of the total accrued MDS trial patient population. Fewer t-MDS patients were accrued in therapeutic trials sponsored by pharmaceutical sponsors vs nonpharmaceutical sponsors (2.8% vs 4.0%; P = .0073). This pattern of exclusion continues in actively enrolling trials; only 5 (10%) of 49 studies specifically mention the inclusion of t-MDS patients in their eligibility criteria. Our results indicate that therapeutic MDS trials seem to exclude t-MDS patients, rendering study results less applicable to this subset of MDS patients, who often have poor outcomes. Our study emphasizes the importance of the recent focus by National Cancer Institute cooperative groups and societies to broaden eligibility criteria for all patients.