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

Background 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. Methods 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). Findings 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; I 2 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; I 2 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 2 0.03; I 2 27%; k=5). Interpretation 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. Funding None.