{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:59:54Z","timestamp":1787313594704,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: High-risk cytogenetic multiple myeloma (HRMM) confers inferior outcomes despite significant therapeutic advances. Real-world data characterizing contemporary treatment patterns across lines of therapy in this population are limited. Methods: We conducted a multicenter retrospective study of 205 patients with HRMM diagnosed between January 2009 and January 2024. High-risk cytogenetics were defined according to the International Myeloma Working Group (IMWG) and Revised International Staging System (R-ISS) criteria as the presence of del(17p), t(4;14), t(14;16), t(14;20), and\/or gain\/amplification of 1q21. Treatment regimens were categorized by the number of agents (doublet, triplet, quadruplet), mechanism of action (proteasome inhibitor [PI]-based, immunomodulatory drug [IMiD]-based, and anti-CD38 monoclonal antibody-based), and specific regimen composition. Treatment patterns were analyzed across three treatment eras and stratified by age (&lt;70 vs. \u226570 years). Results: The cohort included 205 patients (median age, 62 years [interquartile range [IQR], 54\u201368 years]; 78.5% aged &lt;70 years). Double-hit and triple-hit cytogenetics were present in 60.0% and 7.3% of patients, respectively. For first-line induction, triplet therapy predominated (81.0%, n = 166), followed by quadruplet (8.8%, n = 18), doublet (5.9%, n = 12), and multi-agent chemotherapy (2.9%, n = 6). By mechanism of action, PI + IMiD combinations were the most common (63.4%, n = 130), followed by PI-based (19.0%, n = 39), anti-CD38-based (10.2%, n = 21), and IMiD-based (2.9%, n = 6) regimens. Era-stratified analysis revealed a significant increase in quadruplet utilization from 3.2% in Era 1 (2009\u20132015) to 20.3% in Era 3 (2020\u20132024), with anti-CD38-containing frontline regimens administered to 26.6% of patients in the contemporary era (p &lt; 0.001). Second-line induction was required in 50 patients (24.4%), with anti-CD38-based triplets comprising the most common approach (30.0%). Autologous stem cell transplantation (ASCT) was performed in 75.1% of patients overall, with significantly higher utilization in those aged &lt;70 years (83.9% vs. 43.2%). Maintenance therapy was administered to 71.7% of patients (n = 147), with IMiD-based regimens predominating (53.1%), followed by PI + IMiD combinations (27.9%) and anti-CD38-containing regimens (10.2%). Despite intensive therapy, 69.4% of patients on maintenance experienced disease relapse, with higher rates observed in younger patients (74.8% vs. 41.7%). Conclusions: In this real-world HRMM cohort, the PI + IMiD triplet regimen remained the predominant induction approach, with a significant shift toward quadruplet and anti-CD38-containing regimens in the contemporary era. However, substantial relapse rates during maintenance underscore the continued unmet need in HRMM and support the early integration of novel therapeutic strategies, including quadruplet induction and BCMA-directed agents, in this population.<\/jats:p>","DOI":"10.3390\/curroncol33050249","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:12:31Z","timestamp":1777363951000},"page":"249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High-Risk Cytogenetic Multiple Myeloma Remains a Therapeutic Challenge: A 15-Year Real-World Analysis"],"prefix":"10.3390","volume":"33","author":[{"given":"Carmel","family":"Awadallah","sequence":"first","affiliation":[{"name":"Division of Internal Medicine, St John Episcopal Hospital, Far Rockaway, NY 11691, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7537-0112","authenticated-orcid":false,"given":"Anas","family":"Zayad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-7534","authenticated-orcid":false,"given":"Shebli","family":"Atrash","sequence":"additional","affiliation":[{"name":"Levine Cancer Center, Atrium Health, Wake Forest University School of Medicine, Charlotte, NC 28204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7899-7078","authenticated-orcid":false,"given":"Anita","family":"Mazloom","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-4233","authenticated-orcid":false,"given":"Omar","family":"Alkharabsheh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA"},{"name":"Division of Hematology and Oncology, University of Cincinnati, Cincinnati, OH 45219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7464-6898","authenticated-orcid":false,"given":"Prerna","family":"Mewawalla","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, Alleghany Medical Center, Pittsburg, PA 15212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi R.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Blood Disorders, Rutgers Cancer Institute, New Brunswick, NJ 08903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9699-3080","authenticated-orcid":false,"given":"Forat","family":"Lutfi","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3168-2521","authenticated-orcid":false,"given":"Zahra","family":"Mahmoudjafari","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Umair Mushtaq","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9182-3931","authenticated-orcid":false,"given":"Jeries","family":"Kort","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Habib","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-185X","authenticated-orcid":false,"given":"Al-Ola","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1182\/blood-2007-10-078022","article-title":"Multiple myeloma","volume":"111","author":"Kyle","year":"2008","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1182\/blood-2007-10-116129","article-title":"Improved survival in multiple myeloma and the impact of novel therapies","volume":"111","author":"Kumar","year":"2008","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1200\/JCO.2009.26.1610","article-title":"Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: The HOVON 49 Study","volume":"28","author":"Wijermans","year":"2010","journal-title":"J. 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