Zeidan Amer M, Platzbecker Uwe, Bewersdorf Jan Philipp, Stahl Maximilian, Adès Lionel, Borate Uma, Bowen David, Buckstein Rena, Brunner Andrew, Carraway Hetty E, Daver Naval, Díez-Campelo Maria, de Witte Theo, DeZern Amy E, Efficace Fabio, Garcia-Manero Guillermo, Garcia Jacqueline S, Germing Ulrich, Giagounidis Aristoteles, Griffiths Elizabeth A, Hasserjian Robert P, Hellström-Lindberg Eva, Iastrebner Marcelo, Komrokji Rami, Kulasekararaj Austin G, Malcovati Luca, Miyazaki Yasushi, Odenike Olatoyosi, Santini Valeria, Sanz Guillermo, Scheinberg Phillip, Stauder Reinhard, van de Loosdrecht Arjan A, Wei Andrew H, Sekeres Mikkael A, Fenaux Pierre
Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, Yale University, New Haven, CT.
Leipzig University Hospital, Leipzig, Germany.
Blood. 2023 Apr 27;141(17):2047-2061. doi: 10.1182/blood.2022018604.
Myelodysplastic syndromes/myelodysplastic neoplasms (MDS) are associated with variable clinical presentations and outcomes. The initial response criteria developed by the International Working Group (IWG) in 2000 have been used in clinical practice, clinical trials, regulatory reviews, and drug labels. Although the IWG criteria were revised in 2006 and 2018 (the latter focusing on lower-risk disease), limitations persist in their application to higher-risk MDS (HR-MDS) and their ability to fully capture the clinical benefits of novel investigational drugs or serve as valid surrogates for longer-term clinical end points (eg, overall survival). Further, issues related to the ambiguity and practicality of some criteria lead to variability in interpretation and interobserver inconsistency in reporting results from the same sets of data. Thus, we convened an international panel of 36 MDS experts and used an established modified Delphi process to develop consensus recommendations for updated response criteria that would be more reflective of patient-centered and clinically relevant outcomes in HR-MDS. Among others, the IWG 2023 criteria include changes in the hemoglobin threshold for complete remission (CR), the introduction of CR with limited count recovery and CR with partial hematologic recovery as provisional response criteria, the elimination of marrow CR, and specific recommendations for the standardization of time-to-event end points and the derivation and reporting of responses. The updated criteria should lead to a better correlation between patient-centered outcomes and clinical trial results in an era of multiple emerging new agents with novel mechanisms of action.
骨髓增生异常综合征/骨髓增生异常肿瘤（MDS）具有多样的临床表现和预后。国际工作组（IWG）在2000年制定的初始缓解标准已应用于临床实践、临床试验、监管审评及药品标签。尽管IWG标准在2006年和2018年进行了修订（后者侧重于低风险疾病），但在应用于高风险MDS（HR-MDS）时仍存在局限性，且在充分体现新型研究药物的临床获益或作为长期临床终点（如总生存期）的有效替代指标方面能力不足。此外，一些标准的模糊性和实用性相关问题导致解读存在差异，且同一组数据报告结果时观察者间存在不一致性。因此，我们召集了一个由36名MDS专家组成的国际小组，并采用既定的改良德尔菲法，就更新的缓解标准制定共识性建议，这些标准将更能反映HR-MDS中以患者为中心且与临床相关的预后。其中，IWG 2023标准包括完全缓解（CR）血红蛋白阈值的变化、引入计数有限恢复的CR和部分血液学恢复的CR作为临时缓解标准、取消骨髓CR，以及关于事件发生时间终点标准化和缓解推导与报告的具体建议。在多种具有新作用机制的新型药物不断涌现的时代，更新后的标准应能使以患者为中心的预后与临床试验结果之间具有更好的相关性。
