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

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...

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Published in:Blood advances Vol. 4; no. 23; pp. 5988 - 5999
Main Authors: Munshi, Nikhil C., Avet-Loiseau, Herve, Anderson, Kenneth C., Neri, Paola, Paiva, Bruno, Samur, Mehmet, Dimopoulos, Meletios, Kulakova, Margarita, Lam, Annette, Hashim, Mahmoud, He, Jianming, Heeg, Bart, Ukropec, Jon, Vermeulen, Jessica, Cote, Sarah, Bahlis, Nizar
Format: Journal Article
Language:English
Published: United States Elsevier Inc 08.12.2020
American Society of Hematology
Subjects:
Clinical Trials and Observations
Cytogenetics
Humans
Multiple Myeloma - diagnosis
Multiple Myeloma - drug therapy
Neoplasm, Residual
Prognosis
Treatment Outcome
ISSN:2473-9529, 2473-9537, 2473-9537
Online Access:Get full text
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Summary: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. •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. [Display omitted]
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ISSN:2473-9529
2473-9537
2473-9537
DOI:10.1182/bloodadvances.2020002827