Clinical evidence has shown that minimal residual disease (MRD) is an independent prognostic factor of multiple myeloma (MM). MRD negativity has been associated with improved progression-free survival (PFS) and overall survival, and even in patients who do not fully achieve MRD negativity, a decrease in MRD burden is associated with improved PFS. Due to the complexity of MRD characterization and measurement, MRD assessment in MM clinical trials has not been extensively studied.
In a poster presentation at the 2022 International Myeloma Society meeting, Van Oekelen and colleagues presented findings from a systematic review of MRD assessment characteristics in MM trials from 2015 to 2020. A total of 3708 trials were identified through ClinicalTrials.gov and 598 were ultimately included for analysis. A range of clinical trial phases were assessed, from phase 1 through phase 4, including nonrandomized trials. MRD was measured in 145 of the studies (24.2%), and of these, 37.9% were randomized trials, 92.4% included MRD as part of an end point (24.8% of which were included as the primary end point), 6.2% used MRD assessment as a stratification tool, 46.9% did not explicitly state the method of MRD assessment, and 75.2% did not state the detection threshold. Studies that assessed MRD were more likely to be phase 2/3 (P <.001), focused on newly diagnosed MM (P <.001) or maintenance therapy (P = .02), and were more likely to be randomized (P <.001). Overall, an increasing trend of trials including MRD assessment was seen: 13.3% in 2015 to 30.0% in 2020.
Although MRD has been used as an exploratory end point in nonrandomized trials, it is becoming increasingly used in the clinical trial setting. MRD measurement varies in terms of methodology and sensitivity, however, so careful interpretation and understanding of results is important. Although there have been efforts to standardize this process, the use of MRD in clinical practice beyond prognostic assessment is currently limited.
Source:
Van Oekelen O, Birrer N, Wesson W, et al. A systematic review of measurable residual disease (MRD) assessment characteristics in myeloma trials from 2015-2020. Poster presented at: International Myeloma Foundation; August 25-27, 2022; Los Angeles, CA.