Attrition and withdrawal in multiple myeloma randomized controlled trials: A systematic review

作者：Stijn Hentzen, Tomer Meirson, Kelly Koehn, Aaron Michael Goodman, Rajshekhar Chakraborty, Douglas Weston Sborov, Samuel M. Rubinstein, Ghulam Rehman Mohyuddin · 发表于：European Journal Of Haematology · 年份：2023 · DOI：10.1111/ejh.14032 · 被引用次数：3 · 研究领域：Multiple Myeloma Research and Treatments、Cancer Treatment and Pharmacology、Protein Degradation and Inhibitors

OBJECTIVES: Patients with multiple myeloma (MM) enrolled in randomized control trials (RCTs) discontinue treatment for various reasons; however, no prior study has analyzed reasons for discontinuation. We performed a systematic review of MM RCTs to investigate reasons for treatment discontinuation, imbalances between trial cohorts, and reporting practices. METHODS: A comprehensive search for RCTs in MM from 2015 to 2021 identified 45 studies meeting inclusion criteria. RESULTS: Of 21 236 randomized patients, 10 161 (47.8%) discontinued therapy by primary endpoint ascertainment. Causes of discontinuation included progression (n = 4790; 22.6% of randomized patients); toxicity (n = 2569; 12.1%); patient/physician withdrawal (n = 1200; 5.7%) and death (n = 495; 2.3%). Of randomized patients, 20 914 (98.5%) were included in the RCT analysis. Imbalances of attrition, defined as trials with greater than 5% absolute difference in discontinuation rate for reasons other than death, progression, and toxicity between intervention and control arms, were found in 11 (24.4%) studies. CONCLUSIONS: Although progression is the most common reason for RCT treatment discontinuation in patients with MM, over 10% discontinued due to toxicity. Furthermore, 24.4% of trials showed substantial imbalances between trial cohorts; raising concern for informative censoring and emphasizes the importance of detailed characterization of withdrawal in MM RCTs.