Frontiers in oncology · 2026
Temporal and clinical heterogeneity of double M-protein multiple myeloma: diagnostic and treatment-emergent phenotypes.
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Chen D, Yao F
Аннотация
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.
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.