Department of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR.
Department of Cancer Biostatistics, Cleveland Clinic, Cleveland, OH.
Blood Adv. 2019 Sep 24;3(18):2738-2747. doi: 10.1182/bloodadvances.2019000293.
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%; = .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.
治疗相关骨髓增生异常综合征（t-MDS）定义为先前接触化疗或放疗后发生的 MDS，占所有 MDS 诊断的 10%至 20%。t-MDS 患者往往比初发 MDS 患者具有更高的风险疾病和更差的结局，并且通常被排除在治疗性临床试验之外。为了进一步探讨这一问题，我们从 1999 年至 2018 年在 ClinicalTrials.gov 上提取了所有状态类型的临床试验，研究未经治疗的 MDS 患者。使用这些特定的搜索标准，我们根据研究状态、治疗指征、入选标准和赞助商类型分析了 317 项治疗性 MDS 试验，以检查这些因素是否影响 t-MDS 患者的纳入。只有 18 项研究（5.7%）共招募了 231 名 t-MDS 患者，占总招募的 MDS 试验患者人群的 3.2%。制药赞助商赞助的治疗性试验中招募的 t-MDS 患者较少，而非制药赞助商赞助的试验则较多（2.8%对 4.0%； =.0073）。这种排除模式在正在招募的试验中继续存在；只有 49 项研究中的 5 项（10%）在其入选标准中特别提到包括 t-MDS 患者。我们的结果表明，治疗性 MDS 试验似乎排除了 t-MDS 患者，使研究结果对这部分 MDS 患者的适用性降低，这些患者的结局往往较差。我们的研究强调了美国国立癌症研究所合作小组和协会最近关注扩大所有患者入选标准的重要性。
