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Munshi NC, Avet-Loiseau H, Rawstron AC, et al. Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis. JAMA Oncol. 2017;3(1):28–35. doi:10.1001/jamaoncol.2016.3160
What is the utility of minimal residual disease (MRD) assessment in predicting survival outcomes in patients with newly diagnosed multiple myeloma (MM)?
In a meta-analysis of published literature (1990-2016) achievement of MRD-negative status following treatment was associated with a significant improvement in progression-free survival (hazard ratio [HR], 0.41; 95% CI, 0.36-0.48; N = 1273). Overall survival was also significantly prolonged in MRD-negative patients (HR, 0.57; 95% CI, 0.46-0.71; N = 1100). Focusing on patients achieving conventional complete response, MRD-negative status showed similar improvement in survival.
This large-cohort meta-analysis identifies MRD status as a marker of long-term survival outcome in patients with MM and provides evidence to support the integration of MRD assessment as an end point in clinical trials.
Numerous studies have evaluated the prognostic value of minimal residual disease (MRD) in patients with multiple myeloma (MM). Most studies were small and varied in terms of patient population, treatment, and MRD assessment methods.
To evaluate the utility of MRD detection in patients with newly diagnosed MM.
A Medline search was conducted for articles published in English between January 1990 and January 2016.
Eligible studies reported MRD status and progression-free survival (PFS) or overall survival (OS) in 20 or more patients following treatment. Among 405 articles identified, 21 met the initial eligibility criteria and were included in the analysis.
Data Extraction and Synthesis
Information on patient characteristics, treatment, MRD assessment, and outcomes were extracted using a standard form.
Main Outcomes and Measures
The impact of MRD status on PFS and OS was assessed by pooling data from relevant trials. Data were adjusted to allow for different proportions of patients with MRD in different studies, and analyzed using the Peto method. Forest plots were created based on Cox model analysis. Other prespecified research questions were addressed qualitatively.
Fourteen studies (n = 1273) provided data on the impact of MRD on PFS, and 12 studies (n = 1100) on OS. Results were reported specifically in patients who had achieved conventional complete response (CR) in 5 studies for PFS (n = 574) and 6 studies for OS (n = 616). An MRD-negative status was associated with significantly better PFS overall (hazard ratio [HR], 0.41; 95% CI, 0.36-0.48; P < .001) and in studies specifically looking at CR patients (HR, 0.44; 95% CI, 0.34-0.56; P < .001). Overall survival was also favorable in MRD-negative patients overall (HR, 0.57; 95% CI, 0.46-0.71; P < .001) and in CR patients (HR, 0.47; 95% CI, 0.33-0.67; P < .001). Tests of heterogeneity found no significant differences among the studies for PFS and OS.
Conclusions and Relevance
Minimal residual disease-negative status after treatment for newly diagnosed MM is associated with long-term survival. These findings provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of MM.
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