{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:05:05Z","timestamp":1789707905223,"version":"4.0.1"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u00a0=\u00a00.705). In treatment-emergent cases, M-protein decreased from 24.67 to 5.34 g\/L at secondary-component recognition (paired P\u00a0=\u00a00.002), 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\u00a0=\u00a00.297), 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\u00a0=\u00a00.403). 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1910010","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:30:13Z","timestamp":1789705813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal and clinical heterogeneity of double M-protein multiple myeloma: diagnostic and treatment-emergent phenotypes"],"prefix":"10.3389","volume":"16","author":[{"given":"Dangui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center of Anhui Medical University","place":["Anqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center of Anhui Medical University","place":["Anqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)30206-6","article-title":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","volume":"17","author":"Kumar","year":"2016","journal-title":"Lancet Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24319","article-title":"Clinical characteristics and outcomes in biclonal gammopathies","volume":"91","author":"Mullikin","year":"2016","journal-title":"Am J 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monoclonal spike characterized as double monoclonal gammopathy in a patient with multiple myeloma: a rare finding","volume":"67","author":"Saijpaul","year":"2024","journal-title":"Indian J Pathol Microbiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2021-0399","article-title":"Monitoring the M-protein of multiple myeloma patients treated with a combination of monoclonal antibodies: the laboratory solution to eliminate interference","volume":"59","author":"Noori","year":"2021","journal-title":"Clin Chem Lab Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13122933","article-title":"Mass spectrometry profiling of therapeutic antibodies in multiple myeloma: m\/z features and concordance with immunofixation electrophoresis","volume":"13","author":"Pello","year":"2025","journal-title":"Biomedicines"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-0649","article-title":"A personalized mass spectrometry-based assay to monitor M-protein in patients with multiple myeloma (EasyM)","volume":"27","author":"Liyasova","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1200\/JCO-26-01346","article-title":"Peripheral measurable residual disease activity assessment by MALDI-TOF mass spectrometry in patients with newly diagnosed multiple myeloma in the phase III GMMG-HD7 trial","volume":"44","author":"Jin","year":"2026","journal-title":"J Clin Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejro.2025.100675","article-title":"Evaluation of assumed tumour volume in multiple myeloma using dual-energy spectral CT and its correlation between haematological findings","volume":"15","author":"Kosaka","year":"2025","journal-title":"Eur J Radiol Open"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1529678","article-title":"Association of ANA and SSA autoantibodies with progression-free survival in 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