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.
Competing Interests: Declarations. Conflict of interest: FE: had a consultancy or advisory role for AbbVie, Incyte, Syros, Novartis and JAZZ Pharmaceuticals, outside the submitted work. RC: Consulting/Advisory Board-Janssen, Sanofi Pasteur, and Adaptive Biotech. ED is employed by Myeloma Patients Europe which receives grant funding and consultancy fees from pharmaceutical companies and public sources. None of the other authors report any conflicts of interest. Declaration of generative AI and AI-assisted technologies in the writing process: During the preparation of this work the author(s) did not use any AI technology.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)