Hirano Satoshi, Hanada Keisuke, Maeda Hideki
Regulatory Science, Graduate School of Pharmaceutical Science, Meiji Pharmaceutical University, Tokyo, Japan.
Graduate School of Engineering, Osaka University, Osaka, Japan.
Sci Rep. 2025 Jun 2;15(1):19300. doi: 10.1038/s41598-025-05053-6.
Confirming the patient benefit of progression-free survival (PFS) in B-cell non-Hodgkin lymphoma (B-NHL) and multiple myeloma (MM) has become increasingly challenging due to the improved outcomes brought by novel therapies. In parallel, the U.S. Food and Drug Administration recommends conducting randomized trials, focusing on evaluating early endpoints to compare study and control arms for accelerated approval (AA). From both the clinical and regulatory perspectives, identifying early surrogate endpoints for PFS is imperative. In principle, the complete response rate (CRR) is a potential early endpoint for granting AA. This study aimed to evaluate whether the CRR is a surrogate early endpoint for PFS in patients with B-cell malignancies. We investigated the results of randomized trials with data on CRR and PFS using a combined approach of PubMed and Clinical Trial.gov (CTG), identifying 52 trials after applying exclusion criteria. A meta-regression plot showed a significant correlation between the CRR and PFS with an R-squared of 0.822 in 13 trials of aggressive B-NHL, 0.941 in the 8 trials of indolent N-NHL and 0.492 in the 31 trials of MM. This meta-analysis suggests that the CRR can be considered an early surrogate endpoint for PFS in B-NHL and MM.
由于新型疗法带来的疗效改善，要证实无进展生存期（PFS）对B细胞非霍奇金淋巴瘤（B-NHL）和多发性骨髓瘤（MM）患者的益处变得越来越具有挑战性。与此同时，美国食品药品监督管理局建议开展随机试验，重点评估早期终点，以比较研究组和对照组，用于加速批准（AA）。从临床和监管角度来看，确定PFS的早期替代终点势在必行。原则上，完全缓解率（CRR）是授予AA的一个潜在早期终点。本研究旨在评估CRR是否为B细胞恶性肿瘤患者PFS的替代早期终点。我们使用PubMed和临床试验.gov（CTG）的联合方法，调查了具有CRR和PFS数据的随机试验结果，在应用排除标准后确定了52项试验。荟萃回归图显示，在13项侵袭性B-NHL试验中，CRR与PFS之间存在显著相关性，决定系数R²为0.822；在8项惰性N-NHL试验中为0.941；在31项MM试验中为0.492。这项荟萃分析表明，CRR可被视为B-NHL和MM中PFS的早期替代终点。
