Patient-reported outcome domains in multiple myeloma randomized controlled trials and association with survival outcomes

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.