Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed.

在 3 期试验中，总生存期 （OS） 的测量仍然是解释新疗法对多发性骨髓瘤影响的金标准。然而，随着结局的改善，如果要确保新药的及时批准以使患者获得最大益处，那么使用 OS 作为主要终点变得越来越具有挑战性。OS 的替代终点，例如无进展生存期 （PFS） 和对治疗的反应，有助于美国食品药品监督管理局 （FDA） 和欧洲药品管理局 （European Medicines Agency） 作为证明临床益处的终点做出决定，FDA 最近支持使用微小残留病 （MRD） 作为多发性骨髓瘤的加速批准终点。本综述旨在解决使用 PFS 作为替代终点需要仔细解释的情况，特别是对于特定的患者亚组，并考虑确保研究可以设计以解释 PFS 和 OS 之间可能存在的不一致的方法。还讨论了亚组分析的效用，包括那些未预先指定的分析，以确定新药物的目标人群的潜力。