ArticleFrontiers in oncology2026
Temporal and clinical heterogeneity of double M-protein multiple myeloma: diagnostic and treatment-emergent phenotypes.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Double M-protein multiple myeloma (DMP-MM) is an uncommon phenotype characterized by more than one detectable monoclonal component on serum protein electrophoresis and/or immunofixation electrophoresis. Its clinical significance is uncertain, particularly when a secondary component appears after therapy. Methods: We retrospectively studied 21 patients with DMP-MM treated at Anqing Municipal Hospital. Patients were classified as diagnostic DMP-MM when double M-protein was present at diagnosis (n=10) or treatment-emergent DMP-MM when a secondary component appeared after therapy (n=11). M-protein patterns, treatment response, progression-free survival (PFS), overall survival (OS), and exploratory Cox models were analyzed from double M-protein recognition. In treatment-emergent cases, pre-treatment M-protein and bone-marrow flow-cytometric minimal residual disease (MRD; sensitivity 10^-5) at secondary-component detection were also evaluated. All analyses were exploratory. Results: Median age was 66 years (range, 51-84). At initial diagnosis, M-protein was comparable between diagnostic and later treatment-emergent DMP-MM (34.58 vs 24.67 g/L; P = 0.705). In treatment-emergent cases, M-protein decreased from 24.67 to 5.34 g/L at secondary-component recognition (paired P = 0.002), indicating a treatment- and timing-related effect. The newly appearing component had a median concentration of 1.41 g/L (range, 0.39-23.18). PFS events occurred in 8/10 diagnostic and 5/11 treatment-emergent cases; deaths occurred in 6/10 and 4/11, respectively. Two-year PFS was 40.0% (95% CI, 12.3%-67.0%) versus 62.3% (95% CI, 27.7%-84.0%; log-rank P = 0.297), and 2-year OS was 48.0% (95% CI, 16.1%-74.5%) versus 72.7% (95% CI, 37.1%-90.3%; log-rank P = 0.403). Cox estimates were imprecise for PFS (HR 0.557, 95% CI 0.181-1.712) and OS (HR 0.586, 95% CI 0.165-2.084). Conclusions: Diagnostic and treatment-emergent DMP-MM represent different temporal clinical contexts rather than exchangeable biological groups. Lower M-protein burden at treatment-emergent recognition largely reflects prior therapy and measurement timing. Diagnostic DMP-MM showed a numerically less favorable post-recognition survival trajectory, whereas treatment-emergent secondary M-protein did not show an adverse prognostic signal. Component kinetics, MRD context, and treatment exposure should guide interpretation.
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