Shah Darshi, Sparano Francesco, Luo Catherine, Krepper Daniela, Giesinger Johannes M, Baldi Thomas, Duncan Eilidh, Pe Madeline, Chakraborty Rajshekhar, Efficace Fabio
Renaissance School of Medicine at Stony, Brook University, Stony Brook, NY, 11790, USA.
Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy.
Ann Hematol. 2024 Dec;103(12):5849-5859. doi: 10.1007/s00277-024-06129-5. Epub 2024 Dec 7.
Patient-reported outcomes (PROs) are crucial endpoints in multiple myeloma (MM) randomized controlled trials (RCTs), yet there is significant variability in their methodology and reporting. Our study aimed to (a) identify the most commonly pre-specified PRO domains in MM RCTs and those most responsive to modern therapies, and (b) examine the association between PROs and progression-free survival (PFS)/overall survival (OS). We performed a systematic review of MM RCTs that used EORTC QLQ-C30 and published between 01/2014-06/2023. The association between PFS/OS and PRO was explored using Fisher's exact test or Pearson's Chi-squared test. Thirty-five RCTs were identified, with PROs as secondary or exploratory endpoints in all studies. About one-third of RCTs (n=11, 31.4%) pre-specified at least one EORTC QLQ-C30 domain, with the most common domains being Global health status/Quality of life (GHS/QoL) (n = 10, 90.9%), Physical Functioning (n = 6, 54.5%), Fatigue (n = 6, 54.5%), and Pain (n = 6, 54.5%). A statistically significant and/or clinically meaningful difference in at least one EORTC QLQ-C30 domain between arms was seen in 23/35 trials (65.7%), with the most common domains showing improvement being GHS/QoL (12/23 trials), Pain (11/23 trials), Fatigue (9/23 trials), and Physical Functioning (9/23 trials). PRO was noted to be concordant with PFS in 19/33 (57.6%) trials (p = 0.398), and with OS in 22/31 (71%) trials (p = 0.018). Our study identified key PRO domains that can be potentially used as primary endpoint in MM RCTs. Additionally, significant association between PROs and OS highlight the importance of integrating PROs to better capture treatment efficacy.
患者报告结局（PROs）是多发性骨髓瘤（MM）随机对照试验（RCTs）中的关键终点，但在其方法和报告方面存在显著差异。我们的研究旨在：（a）确定MM随机对照试验中最常预先指定的PRO领域以及对现代疗法反应最敏感的领域；（b）研究PROs与无进展生存期（PFS）/总生存期（OS）之间的关联。我们对2014年1月至2023年6月期间使用欧洲癌症研究与治疗组织核心生活质量问卷（EORTC QLQ-C30）的MM随机对照试验进行了系统评价。使用Fisher精确检验或Pearson卡方检验探讨PFS/OS与PRO之间的关联。共识别出35项随机对照试验，所有研究中PROs均作为次要或探索性终点。约三分之一的随机对照试验（n = 11，31.4%）预先指定了至少一个EORTC QLQ-C30领域，最常见的领域是总体健康状况/生活质量（GHS/QoL）（n = 10，90.9%）、身体功能（n = 6，54.5%）、疲劳（n = 6，54.5%）和疼痛（n = 6，54.5%）。在23/35项试验（65.7%）中，各治疗组之间至少有一个EORTC QLQ-C30领域存在统计学显著差异和/或具有临床意义的差异，显示出改善的最常见领域是GHS/QoL（12/23项试验）、疼痛（11/23项试验）、疲劳（9/23项试验）和身体功能（9/23项试验）。在19/33项（57.6%）试验中（p = 0.398），PRO与PFS一致，在22/31项（71%）试验中（p = 0.018），PRO与OS一致。我们的研究确定了可潜在用作MM随机对照试验主要终点的关键PRO领域。此外，PROs与OS之间的显著关联突出了整合PROs以更好地评估治疗效果的重要性。
