Abrisqueta Pau, Jiménez-Ubieto Ana, Serna Ángel, Zamanillo Irene, Kuang Yuting, Uyei Jennifer, Shah Mohsin, Walsh Laura, Thorley Eileen, Cantos Krystal, Rashidi Emaan, Ma Qiufei, Jalbert Jessica J, Archambault Alexi N, Xu Yingxin, Aggarwal Shivani, Ambati Srikanth, Mohamed Hesham, Hampp Christian, von Tresckow Bastian
Department of Hematology, Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Hematology Department, University Hospital 12 de Octubre, Madrid, Spain.
Ann Hematol. 2025 Sep 2. doi: 10.1007/s00277-025-06575-9.
To enhance the quality of real-world external comparative studies, it is essential to systematically identify, prespecify, and account for prognostic variables and effect measure modifiers (EMMs), especially between emulated target trial and real-world control arms. These factors can then be utilized to evaluate cohort comparability and perform covariate adjustments, such as in propensity score models. A systematic literature review (SLR)-based identification of prognostic factors, coupled with expert clinical review, offers a comprehensive approach to evaluating and ranking the level of evidence, while also assisting in selection of prognostic factors to assess imbalances between cohorts in single-arm trials and real-world data studies. We performed an SLR followed by a clinical review and ranking by subject-matter experts to identify prognostic factors and EMMs in patients with relapsed or refractory (r/r) follicular lymphoma (FL) who failed at least two lines of therapy (LoTs). Across 13 included studies, the SLR identified 28 prognostic factors that were significantly associated with clinical outcomes, including overall survival, progression-free survival, and objective response rate. Notably, our review did not identify any statistically significant EMMs. Based on expert ranking of the SLR-derived list, the 5 most important prognostic variables in descending order are: progression of disease within 24 months of first LoT (POD24), chemo-immunorefractory/chemoresistant, refractory to last LoT, number of prior LoTs, and serum lactate dehydrogenase. This comprehensive SLR and expert review highlight critical prognostic factors in r/r FL. The identified prognostic variables can inform future research, emphasizing the need for continued investigation into factors affecting outcomes in this challenging and heterogeneous patient population.
为提高真实世界外部比较研究的质量,系统地识别、预先设定并考虑预后变量和效应测量修饰因素(EMM)至关重要,尤其是在模拟目标试验与真实世界对照臂之间。然后可以利用这些因素评估队列可比性并进行协变量调整,如在倾向评分模型中。基于系统文献综述(SLR)识别预后因素,并结合专家临床审查,提供了一种全面的方法来评估和分级证据水平,同时也有助于选择预后因素以评估单臂试验和真实世界数据研究中各队列之间的不平衡。我们进行了一项SLR,随后进行临床审查并由主题专家进行排名,以识别至少接受过两线治疗(LoT)失败的复发或难治性(r/r)滤泡性淋巴瘤(FL)患者的预后因素和EMM。在纳入的13项研究中,SLR识别出28个与临床结局显著相关的预后因素,包括总生存期、无进展生存期和客观缓解率。值得注意的是,我们的综述未发现任何具有统计学意义的EMM。根据对SLR得出的列表进行的专家排名,按重要性降序排列的5个最重要的预后变量为:首次LoT后24个月内疾病进展(POD24)、化疗免疫难治/化疗耐药、对最后一次LoT难治、既往LoT次数和血清乳酸脱氢酶。这项全面的SLR和专家审查突出了r/r FL中的关键预后因素。所识别的预后变量可为未来研究提供参考,强调需要继续研究影响这一具有挑战性的异质性患者群体结局的因素。
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