{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:14:51Z","timestamp":1791864891551,"version":"4.3.4"},"reference-count":26,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Society of Hematology","award":["282"],"award-info":[{"award-number":["282"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) is a biologically heterogeneous plasma cell malignancy in which prognosis is strongly influenced by cytogenetic abnormalities. Recent updates from the International Myeloma Working Group (IMWG), along with the European Hematology Association (EHA) and European Myeloma Network (EMN), have refined the definition of high-risk (HR) disease by integrating TP53 alterations, chromosome 1 abnormalities, and specific combinations of cytogenetic lesions. However, validation of these criteria in real-world patient populations remains limited. We conducted a retrospective, single-center study including 738 patients diagnosed with MM between 2017 and 2025, of whom 408 had available fluorescence in situ hybridization (FISH) data at diagnosis. Patients were reclassified according to the latest IMWG\/IMS high-risk criteria proposed in international literature. Cytogenetic abnormalities, treatment patterns, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rates, and relapse, were analyzed. Survival was estimated using the Kaplan\u2013Meier method. A total of 103 patients (25%) were reclassified as high-risk according to IMWG\/IMS high-risk criteria. Cytogenetic HR abnormalities were identified in 17.2% of cases, with del(17p) being the most frequent (14.7%). Median OS and PFS in HR patients were 52.4 months and 16 months, respectively, compared with 68.4 months and 28 months in standard-risk patients (log-rank test p values of 0.0197 and 0.0004, respectively). Although overall response rates were high (83% in HR vs. 91% in standard-risk), relapse remained frequent in HR patients. Outcomes varied significantly according to cytogenetic complexity. Isolated del(17p) was associated with improved survival compared with cases harboring additional abnormalities, while double-hit and triple-hit profiles demonstrated inferior outcomes. The presence of chromosome 1 abnormalities, particularly in combination with IGH translocations, further worsened prognosis. Among HR patients, 44% underwent autologous stem cell transplantation (ASCT), including 10 cases of TANDEM ASCT. No survival benefit was observed for TANDEM compared with single ASCT, with median OS of 52.9 vs. 78.3 months, respectively (log-rank test p values of 0.2516). Our real-world analysis supports the prognostic relevance of the updated IMS\/IMWG high-risk criteria in MM. Cytogenetic complexity, rather than individual abnormalities alone, is a key determinant of outcome. Despite high response rates achieved with modern therapies, survival remains inferior in HR patients. TANDEM ASCT did not confer additional benefit in this cohort, supporting a more individualized approach to treatment intensification.<\/jats:p>","DOI":"10.3390\/ijms27104620","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:06:07Z","timestamp":1779365167000},"page":"4620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of the New IMWG\/IMS High-Risk Classification for Multiple Myeloma: Analysis of a Large Real-World Romanian Cohort"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1507-2547","authenticated-orcid":false,"given":"Sorina Nicoleta","family":"Badelita","sequence":"first","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinziana","family":"Barbu","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onda-Tabita","family":"Calugaru","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cerasela","family":"Jardan","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7638-3285","authenticated-orcid":false,"given":"Codruta Delia","family":"Popa","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Zidaru","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai Emanuel","family":"Himcinschi","sequence":"additional","affiliation":[{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"},{"name":"Biochemistry Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan Nicolas","family":"Smadu","sequence":"additional","affiliation":[{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulia","family":"Ursuleac","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Coriu","sequence":"additional","affiliation":[{"name":"Clinical Department I, Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Hematology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-024-00529-7","article-title":"Multiple myeloma","volume":"10","author":"Malard","year":"2024","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","first-page":"27","article-title":"Multiple Myeloma and Solid Tumors\u2014A Frequent Rarity","volume":"2","author":"Cirlan","year":"2024","journal-title":"Doc. Haematol. Rev. Romana Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1200\/JCO.2005.04.242","article-title":"International Staging System for Multiple Myeloma","volume":"23","author":"Greipp","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised international staging system for multiple myeloma: A report from international myeloma working group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1002\/ajh.27422","article-title":"Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management","volume":"99","author":"Rajkumar","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1200\/JCO-24-01893","article-title":"International Myeloma Society\/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma","volume":"43","author":"Davies","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1200\/JCO.21.02614","article-title":"Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project","volume":"40","author":"Cairns","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/s41571-025-01041-x","article-title":"EHA\u2013EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma","volume":"22","author":"Dimopoulos","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"De Novellis, D., Scala, P., Giudice, V., and Selleri, C. (2025). High-Risk Genetic Multiple Myeloma: From Molecular Classification to Innovative Treatment with Monoclonal Antibodies and T-Cell Redirecting Therapies. Cells, 14.","DOI":"10.3390\/cells14110776"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41408-025-01268-y","article-title":"A Real-World International Staging System (RW-ISS) for patients with newly diagnosed multiple myeloma","volume":"15","author":"Brieghel","year":"2025","journal-title":"Blood Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, Y., Liu, J., Deng, J., Jian, Y., Zhang, Z., Zhou, H., Li, J., and Chen, W. (2024). A new prognostic scoring system for newly diagnosed multiple myeloma in the era of new drugs. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1473034"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/jha2.595","article-title":"Real-world use of carfilzomib combined with lenalidomide and dexa-methasone in patients with multiple myeloma in Europe and Israel","volume":"4","author":"Leleu","year":"2023","journal-title":"eJHaem"},{"key":"ref_13","unstructured":"Barbu, S., Irimia, R., Popescu, M., Preda, D., Jercan, A., Coriu, D., and Sorina, B. (2023, May 29). Myelomatous Meningitis\u2014A Diagnostic and Therapeutic Challenge. 2023, Volume 1. Available online: https:\/\/www.dhrrh.ro\/wp-content\/uploads\/2023\/10\/DHRRH_2023_1_Art-02.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e538","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":"ref_15","first-page":"912","article-title":"Adverse effects of double-hit combining ISS-III stage and 1q gain or del (17p) on prognosis of patients with newly diagnosed multiple myeloma","volume":"40","author":"Liu","year":"2019","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1182\/blood.2025029999","article-title":"High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing","volume":"147","author":"Schavgoulidze","year":"2026","journal-title":"Blood"},{"key":"ref_17","first-page":"944","article-title":"Prognostic analysis of 19 newly treated multiple myeloma patients with t(14; 16)","volume":"45","author":"Li","year":"2024","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1182\/blood-2011-09-379164","article-title":"Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p","volume":"119","author":"Neben","year":"2012","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1182\/blood-2020-141783","article-title":"Presence of Multiple High Risk Cytogenetic Abnormalities Is As-sociated with Rapid Progression and Shorter Survival in Newly Diagnosed Multiple Myeloma","volume":"136","author":"Smallbone","year":"2020","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e270045","DOI":"10.1002\/jha2.70045","article-title":"A Single-Center Study on Frontline Treatment for Multiple Myeloma Patients With 1q Abnormalities","volume":"6","author":"Patel","year":"2025","journal-title":"eJHaem"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1007\/s00277-025-06563-z","article-title":"Tandem autologous hematopoietic stem cell transplantation in multiple myeloma: A historical perspective and current challenges","volume":"104","author":"Wang","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1056\/NEJMoa2505133","article-title":"Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma","volume":"393","author":"Perrot","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1001\/jamaoncol.2020.4338","article-title":"Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors: A Systematic Review and Meta-analysis","volume":"6","author":"Giri","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1200\/JCO.22.02567","article-title":"Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, and Dexamethasone as Induction and Extended Consolidation Improves Outcome in Ultra-High-Risk Multiple Myeloma","volume":"41","author":"Kaiser","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1200\/JCO.23.01696","article-title":"Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma","volume":"42","author":"Leypoldt","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.jtct.2024.06.030","article-title":"Tandem Autologous Stem Cell Transplantation Does Not Benefit High-Risk Myeloma Patients in the Maintenance Era: Real-World Results from The Canadian Myeloma Research Group Database","volume":"30","author":"Venner","year":"2024","journal-title":"Transplant. Cell. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:13:02Z","timestamp":1779365582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104620"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104620","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]}}}