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We conducted a retrospective single-center analysis of 86 patients with radiologically confirmed EMD, defined as soft-tissue involvement without bone contiguity (data cut-off September 30, 2024). The cohort included patients with\n                    <jats:italic>de novo<\/jats:italic>\n                    EMD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919, 22%) and\n                    <jats:italic>secondary<\/jats:italic>\n                    EMD at relapse of MM (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200967, 78%). We assessed clinical characteristics, survival outcomes, and treatment strategies. Treatment was highly heterogeneous, comprising\u2009&gt;\u200950 distinct regimens. Median overall survival (mOS) from initial MM diagnosis was 55\u00a0months. mOS from EMD occurrence was 28\u00a0months for\n                    <jats:italic>de novo<\/jats:italic>\n                    and 21\u00a0months for\n                    <jats:italic>secondary<\/jats:italic>\n                    EMD. Survival varied by anatomical site: central nervous system (CNS), pulmonary, and retroperitoneal involvement showed a trend toward inferior survival, whereas lymph node involvement was associated with significantly longer survival in exploratory analyses (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011). Based on these findings, we exploratorily categorized anatomical sites into a three-tiered risk grouping, which revealed a stepwise gradient that did not reach statistical significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.054). High-risk cytogenetic features were present in 50% of patients with\n                    <jats:italic>de novo<\/jats:italic>\n                    EMD and in 43% with\n                    <jats:italic>secondary EMD<\/jats:italic>\n                    . Novel agents, including CAR T-cell therapy and bispecific antibodies, were used predominantly in later lines, with responses in secondary EMD that were often transient. This real-world analysis confirms the high-risk nature of EMD, especially for patients with CNS, pulmonary, or retroperitoneal involvement. Given the observed treatment heterogeneity, prospective registries are urgently needed to define optimal therapeutic sequencing and address the high unmet therapeutic need in EMD patients.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-07118-6","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:24:53Z","timestamp":1781634293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characteristics, treatment regimens, and outcomes of patients with true extramedullary multiple myeloma: a real-world monocentric analysis"],"prefix":"10.1007","volume":"105","author":[{"given":"Marie","family":"Harzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Gross-Fengels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fede","family":"Melzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Molwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Kosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Al-Bazaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jule","family":"Artzenroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Cords","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandra","family":"Bartke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Kamili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Alsdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa B.","family":"Leypoldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schaefers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"issue":"11","key":"7118_CR1","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1056\/NEJMra1011442","volume":"364","author":"A Palumbo","year":"2011","unstructured":"Palumbo A, Anderson K (2011) Multiple myeloma. 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