Concordance and prognostic value of bone-marrow MRD and PET-CT in multiple myeloma: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>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.<h4>Methods</h4>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^-/PET-CT⁺ vs MRD⁺/PET-CT^-), and (2) the prognostic effect of dual negativity (MRD^-/PET-CT^- 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).<h4>Findings</h4>Ten cohorts contributed 1138 paired MRD/PET-CT assessments. The joint 2 × 2 distribution was: (a) MRD^-/PET-CT⁺ 145 (12.7%), (b) MRD^-/PET-CT^- 499 (43.8%), (c) MRD⁺/PET-CT^- 310 (27.2%), and (d) MRD⁺/PET-CT⁺ 184 (16.2%). Observed agreement was 60.0%, and pooled κ was 0.14 (95% CI 0.03-0.25; I² 57%). Discordant results predominantly reflected MRD⁺/PET-CT^- rather than MRD^-/PET-CT⁺ (primary pooled log-odds -0.83, 95% CI -1.87 to 0.21; I² 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); τ² 0.03; I² 27%; k = 5).<h4>Interpretation</h4>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.<h4>Funding</h4>None.