Concordance and prognostic value of bone-marrow MRD and PET-CT in multiple myeloma: a systematic review and meta-analysis.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 42005928.
- Also identified by DOI 10.1016/j.eclinm.2026.103868 and PMC identifier 13090622.
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Abstract
Bone-marrow minimal residual disease (MRD) and positron emission tomography/computed tomography (PET-CT) are central to response assessment in multiple myeloma (MM); however, their agreement, discordant patterns, and how their joint results relate to progression-free survival have not been systematically quantified. We conducted a systematic review and random-effects meta-analysis, and searched PubMed and Cochrane CENTRAL from Jan 2015 to Sept 30, 2025, with an updated search to Jan 31, 2026. We included studies reporting paired MRD and PET-CT assessments, and, when available, progression-free survival (PFS), in patients with MM. Study-level 2 × 2 MRD/PET-CT tables (each test positive or negative) were abstracted or reconstructed from published counts or percentages. Primary outcomes were (1) cross-modality agreement (observed agreement and Cohen's κ) and directional discordance (log-odds of MRD<sup>-</sup>/PET-CT<sup>+</sup> vs MRD<sup>+</sup>/PET-CT<sup>-</sup>), and (2) the prognostic effect of dual negativity (MRD<sup>-</sup>/PET-CT<sup>-</sup> vs all other combinations) on PFS. We used random-effects models (REML with Hartung-Knapp adjustment) to estimate pooled hazard ratios for PFS. Sensitivity analyses were informed by QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and QUIPS (Quality in Prognosis Studies) risk-of-bias assessments. This study was registered with Open Science Framework (OSF; DOI 10.17605/OSF.IO/3CH9E). Ten cohorts contributed 1138 paired MRD/PET-CT assessments. The joint 2 × 2 distribution was: (a) MRD<sup>-</sup>/PET-CT<sup>+</sup> 145 (12.7%), (b) MRD<sup>-</sup>/PET-CT<sup>-</sup> 499 (43.8%), (c) MRD<sup>+</sup>/PET-CT<sup>-</sup> 310 (27.2%), and (d) MRD<sup>+</sup>/PET-CT<sup>+</sup> 184 (16.2%). Observed agreement was 60.0%, and pooled κ was 0.14 (95% CI 0.03-0.25; I<sup>2</sup> 57%). Discordant results predominantly reflected MRD<sup>+</sup>/PET-CT<sup>-</sup> rather than MRD<sup>-</sup>/PET-CT<sup>+</sup> (primary pooled log-odds -0.83, 95% CI -1.87 to 0.21; I<sup>2</sup> 93%; k = 10). In five studies reporting PFS by joint MRD/PET-CT status, dual negativity was associated with substantially longer PFS than all other categories (pooled HR 0.34 (95% CI 0.22-0.51); τ<sup>2</sup> 0.03; I<sup>2</sup> 27%; k = 5). MRD and PET-CT interrogate distinct but complementary disease compartments, yielding low statistical concordance yet strong joint prognostic value. Dual MRD/PET-CT negativity reproducibly identifies a low-risk subgroup, whereas discordant patterns capture biologically heterogeneous residual disease. Prospective myeloma trials should prespecify all four MRD/PET-CT categories, align assessment timing and thresholds, and routinely report concordance and discordance to enable response-adapted treatment. None.