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      A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma

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          Key Points

          • This meta-analysis establishes the role of MRD negativity in improving long-term survival in a heterogeneous cohort of patients with MM.

          • The strong prognostic value of MRD negativity sets the stage to adopt MRD as a clinically valid surrogate biomarker for PFS and OS in MM.

          Abstract

          The prognostic value of minimal residual disease (MRD) for progression-free survival (PFS) and overall survival (OS) was evaluated in a large cohort of patients with multiple myeloma (MM) using a systematic literature review and meta-analysis. Medline and EMBASE databases were searched for articles published up to 8 June 2019, with no date limit on the indexed database. Clinical end points stratified by MRD status (positive or negative) were extracted, including hazard ratios (HRs) on PFS and OS, P values, and confidence intervals (CIs). HRs were estimated based on reconstructed patient-level data from published Kaplan-Meier curves. Forty-four eligible studies with PFS data from 8098 patients, and 23 studies with OS data from 4297 patients were identified to assess the association between MRD status and survival outcomes. Compared with MRD positivity, achieving MRD negativity improved PFS (HR, 0.33; 95% CI, 0.29-0.37; P < .001) and OS (HR, 0.45; 95% CI, 0.39-0.51; P < .001). MRD negativity was associated with significantly improved survival outcomes regardless of disease setting (newly diagnosed or relapsed/refractory MM), MRD sensitivity thresholds, cytogenetic risk, method of MRD assessment, depth of clinical response at the time of MRD measurement, and MRD assessment premaintenance and 12 months after start of maintenance therapy. The strong prognostic value of MRD negativity and its association with favorable outcomes in various disease and treatment settings sets the stage to adopt MRD as a treatment end point, including development of therapeutic strategies. This large meta-analysis confirms the utility of MRD as a relevant surrogate for PFS and OS in MM.

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          Author and article information

          Journal
          Blood Adv
          Blood Adv
          bloodoa
          Blood Adv
          Blood Advances
          Blood Advances
          American Society of Hematology (Washington, DC )
          2473-9529
          2473-9537
          8 December 2020
          07 December 2020
          07 December 2020
          : 4
          : 23
          : 5988-5999
          Affiliations
          [1 ]Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
          [2 ]Veterans Administration Boston Healthcare System, West Roxbury, MA;
          [3 ]Unité de Génomique du Myélome, Institut Universitaire du Cancer de Toulouse (IUC-T) Oncopole, Toulouse, France;
          [4 ]Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada;
          [5 ]Clínica Universidad de Navarra, Pamplona, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) CB16/12/00369, Madrid, Spain;
          [6 ]Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece;
          [7 ]Ingress Health, Rotterdam, The Netherlands;
          [8 ]Janssen Global Services, LLC, Raritan, NJ; and
          [9 ]Janssen Global Medical Affairs, Horsham, PA
          Author information
          https://orcid.org/0000-0002-5775-9590
          https://orcid.org/0000-0002-5015-3713
          Article
          PMC7724898 PMC7724898 7724898 2020/ADV2020002827
          10.1182/bloodadvances.2020002827
          7724898
          33284948
          a72270cb-a9f5-4acd-aad4-3ba8d1644083
          History
          : 29 June 2020
          : 10 September 2020
          Page count
          Pages: 12
          Categories
          20
          24
          Clinical Trials and Observations
          Custom metadata
          free

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