Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis | Allergy and Clinical Immunology | JAMA Oncology | JAMA Network
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Original Investigation
January 2017

Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis

Author Affiliations
  • 1Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • 2Unit for Genomics in Myeloma, Institut Universitaire du Cancer, Toulouse, France
  • 3St James's University Hospital, Leeds, United Kingdom
  • 4University of Leeds, Leeds, United Kingdom
  • 5Celgene Corporation, Summit, New Jersey
  • 6Celgene International, Boudry, Switzerland
  • 7Excerpta Medica, Amsterdam, the Netherlands
JAMA Oncol. 2017;3(1):28-35. doi:10.1001/jamaoncol.2016.3160
Key Points

Question  What is the utility of minimal residual disease (MRD) assessment in predicting survival outcomes in patients with newly diagnosed multiple myeloma (MM)?

Findings  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.

Meaning  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.

Abstract

Importance  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.

Objective  To evaluate the utility of MRD detection in patients with newly diagnosed MM.

Data Sources  A Medline search was conducted for articles published in English between January 1990 and January 2016.

Study Selection  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.

Results  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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