{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:51Z","timestamp":1787027871058,"version":"build-2736575974"},"reference-count":114,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>High-risk genetic multiple myeloma (HRMM) remains a major therapeutic challenge, as patients harboring adverse genetic abnormalities, such as del(17p), TP53 mutations, and biallelic del(1p32), continue to experience poor outcomes despite recent therapeutic advancements. This review explores the evolving definition and molecular features of HRMM, focusing on recent updates in risk stratification and treatment strategies. The new genetic classification proposed at the 2025 EMMA meeting offers improved prognostic accuracy and supports more effective, risk-adapted treatment planning. In transplant-eligible patients, intensified induction regimens, tandem autologous stem cell transplantation, and dual-agent maintenance have shown improved outcomes, particularly when sustained minimal residual disease negativity is achieved. Conversely, in the relapsed or refractory setting, novel agents have demonstrated encouraging activity, although their specific efficacy in HRMM is under investigation. Moreover, treatment paradigms are shifting toward earlier integration of immunotherapy, and therapeutic strategies are individualized based on refined molecular risk profiles and clone dynamics. Therefore, a correct definition of HRMM could help in significantly improving both clinical and therapeutic management of a subgroup of patients with an extremely aggressive disease.<\/jats:p>","DOI":"10.3390\/cells14110776","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:39:36Z","timestamp":1748205576000},"page":"776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["High-Risk Genetic Multiple Myeloma: From Molecular Classification to Innovative Treatment with Monoclonal Antibodies and T-Cell Redirecting Therapies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2590-0529","authenticated-orcid":false,"given":"Danilo","family":"De Novellis","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"},{"name":"Hematology and Transplant Center, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasqualina","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"},{"name":"Hematology and Transplant Center, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-6848","authenticated-orcid":false,"given":"Valentina","family":"Giudice","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"},{"name":"Hematology and Transplant Center, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5861-8984","authenticated-orcid":false,"given":"Carmine","family":"Selleri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"},{"name":"Hematology and Transplant Center, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Novellis, D., Fontana, R., Carobene, A., Serio, B., Ferrara, I., Martorelli, M.C., Mettivier, L., Guariglia, R., Luponio, S., and Ruggiero, I. (2022). Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071657"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1182\/bloodadvances.2016002493","article-title":"Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States","volume":"1","author":"Costa","year":"2017","journal-title":"Blood Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1182\/blood-2016-01-631200","article-title":"Treatment of multiple myeloma with high-risk cytogenetics: A consensus of the International Myeloma Working Group","volume":"127","author":"Sonneveld","year":"2016","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1200\/JCO.2016.70.6705","article-title":"Genomics of Multiple Myeloma","volume":"35","author":"Cleynen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1182\/blood-2015-06-650242","article-title":"Understanding the role of hyperdiploidy in myeloma prognosis: Which trisomies really matter?","volume":"126","author":"Chretien","year":"2015","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1182\/blood-2002-10-3017","article-title":"Clinical and biologic implications of recurrent genomic aberrations in myeloma","volume":"101","author":"Fonseca","year":"2003","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1182\/blood.2020008733","article-title":"How I treat high-risk multiple myeloma","volume":"139","author":"Zamagni","year":"2022","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1182\/blood-2006-03-009910","article-title":"Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: Incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation","volume":"108","author":"Hanamura","year":"2006","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1002\/ajh.25994","article-title":"The prognostic value of additional copies of 1q21 in multiple myeloma depends on the primary genetic event","volume":"95","author":"Locher","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41408-021-00474-8","article-title":"Chromosome 1q21 abnormalities in multiple myeloma","volume":"11","author":"Schmidt","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/leu.2013.225","article-title":"Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: The IFM experience on 1195 patients","volume":"28","author":"Hebraud","year":"2013","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1182\/blood.2022017863","article-title":"Biallelic deletion of 1p32 defines ultra-high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor","volume":"141","author":"Schavgoulidze","year":"2023","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1182\/blood.2020008346","article-title":"del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma","volume":"137","author":"Corre","year":"2021","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1182\/blood-2018-10-880831","article-title":"High subclonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma","volume":"133","author":"Thakurta","year":"2019","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1200\/JCO.18.00776","article-title":"Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma","volume":"37","author":"Perrot","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1182\/bloodadvances.2022009387","article-title":"Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells","volume":"7","author":"Chang","year":"2023","journal-title":"Blood Adv."},{"key":"ref_17","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_18","unstructured":"(2025, April 26). Available online: https:\/\/emma-vienna.org\/sites\/default\/files\/EMMA-2025_Booklet-web.pdf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nrc.2017.63","article-title":"Evolutionary biology of high-risk multiple myeloma","volume":"17","author":"Pawlyn","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41408-023-00919-2","article-title":"Identifying novel mechanisms of biallelic TP53 loss refines poor outcome for patients with multiple myeloma","volume":"13","author":"Liu","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s00277-025-06212-5","article-title":"Overview of 1q abnormalities in multiple myeloma: Scientific opinions from Italian experts","volume":"104","author":"Martello","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1038\/bcj.2012.37","article-title":"The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: Prognostic implications and current clinical strategies","volume":"2","author":"Kalff","year":"2012","journal-title":"Blood Cancer J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Suzuki, K., and Yano, S. (2023). Treatment Strategy for Ultra-High-Risk Multiple Myelomas with Chromosomal Aberrations Considering Minimal Residual Disease Status and Bone Marrow Microenvironment. Cancers, 15.","DOI":"10.3390\/cancers15092418"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10238-024-01313-3","article-title":"Non-invasive prenatal test identifies circulating cell-free DNA chromosomal abnormalities derived from clonal hematopoiesis in aggressive hematological malignancies","volume":"24","author":"Giudice","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.beha.2007.08.004","article-title":"Genetic events in the pathogenesis of multiple myeloma","volume":"20","author":"Chng","year":"2007","journal-title":"Best. Pract. Res. Clin. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/ajh.27327","article-title":"High-risk multiple myeloma: Redefining genetic, clinical, and functional high-risk disease in the era of molecular medicine and immunotherapy","volume":"99","author":"Rees","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Solimando, A.G., Da Vi\u00e0, M.C., Cicco, S., Leone, P., Di Lernia, G., Giannico, D., DeSantis, V., Frassanito, M.A., Morizio, A., and Delgado Tascon, J. (2019). High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment. J. Clin. Med., 8.","DOI":"10.20944\/preprints201906.0145.v1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.18632\/oncotarget.1497","article-title":"Drug resistance in multiple myeloma: Latest findings and new concepts on molecular mechanisms","volume":"4","author":"Abdi","year":"2013","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Awada, H., Thapa, B., Awada, H., Dong, J., Gurnari, C., Hari, P., and Dhakal, B. (2021). A Comprehensive Review of the Genomics of Multiple Myeloma: Evolutionary Trajectories, Gene Expression Profiling, and Emerging Therapeutics. Cells, 10.","DOI":"10.3390\/cells10081961"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.leukres.2011.02.010","article-title":"Evolutionary sequence of cytogenetic aberrations during the oncogenesis of plasma cell disorders. Direct evidence at single cell level","volume":"35","author":"Nagy","year":"2011","journal-title":"Leuk. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nrclinonc.2016.122","article-title":"Genomic complexity of multiple myeloma and its clinical implications","volume":"14","author":"Manier","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1182\/blood-2007-05-088674","article-title":"The multiple myeloma\u2013associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity","volume":"111","author":"Lauring","year":"2008","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5630","DOI":"10.1038\/sj.onc.1206636","article-title":"Regulation of FGF receptor-2 expression by transcription factor E2F-1","volume":"22","author":"Tashiro","year":"2003","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1007\/s00018-019-03144-y","article-title":"Understanding histone H3 lysine 36 methylation and its deregulation in disease","volume":"76","author":"Li","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"De Smedt, E., Lui, H., Maes, K., De Veirman, K., Menu, E., Vanderkerken, K., and De Bruyne, E. (2018). The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00566"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3324\/haematol.13426","article-title":"MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells","volume":"94","author":"Brito","year":"2009","journal-title":"Haematologica"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1007\/s12185-022-03353-5","article-title":"Multiple myeloma with high-risk cytogenetics and its treatment approach","volume":"115","author":"Hanamura","year":"2022","journal-title":"Int. J. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1182\/blood-2016-03-706077","article-title":"MAF protein mediates innate resistance to proteasome inhibition therapy in multiple myeloma","volume":"128","author":"Qiang","year":"2016","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1182\/blood.2023019758","article-title":"Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis","volume":"142","author":"Poos","year":"2023","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1021\/acsptsci.4c00208","article-title":"Development of Epigenetic Modifiers with Therapeutic Potential in FMS-Related Tyrosine Kinase 3\/Internal Tandem Duplication (FLT3\/ITD) Acute Myeloid Leukemia and Other Blood Malignancies","volume":"7","author":"Carullo","year":"2024","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.dnarep.2006.05.012","article-title":"Distinguishing primary and secondary translocations in multiple myeloma","volume":"5","author":"Gabrea","year":"2006","journal-title":"DNA Repair."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3324\/haematol.2009.012864","article-title":"Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma","volume":"95","author":"Stasik","year":"2010","journal-title":"Haematologica"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/modpathol.2012.75","article-title":"The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanoma","volume":"25","author":"Pouryazdanparast","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1182\/blood.V128.22.3266.3266","article-title":"Concurrent Amplification of MYC and 1q21 in Multiple Myeloma: Focal and Segmental Jumping Translocations of MYC","volume":"128","author":"Sawyer","year":"2016","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hanamura, I. (2021). Gain\/Amplification of Chromosome Arm 1q21 in Multiple Myeloma. Cancers, 13.","DOI":"10.3390\/cancers13020256"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.gendis.2022.12.020","article-title":"The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities","volume":"11","author":"Yang","year":"2024","journal-title":"Genes. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"180","DOI":"10.14336\/AD.2015.0929","article-title":"Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases","volume":"7","author":"Antero","year":"2016","journal-title":"Aging Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7776","DOI":"10.1158\/1078-0432.CCR-11-1791","article-title":"Mapping of Chromosome 1p Deletions in Myeloma Identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as Being Genes in Regions Associated with Adverse Survival","volume":"17","author":"Boyd","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bonelli, P., Tuccillo, F.M., Borrelli, A., Schiattarella, A., and Buonaguro, F.M. (2014). CDK\/CCN and CDKI Alterations for Cancer Prognosis and Therapeutic Predictivity. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/361020"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Medina-Herrera, A., Sarasquete, M.E., Jim\u00e9nez, C., Puig, N., and Garc\u00eda-Sanz, R. (2023). Minimal Residual Disease in Multiple Myeloma: Past, Present, and Future. Cancers, 15.","DOI":"10.3390\/cancers15143687"},{"key":"ref_52","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_53","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1200\/JCO.2013.54.8164","article-title":"Front-Line Transplantation Program With Lenalidomide, Bortezomib, and Dexamethasone Combination As Induction and Consolidation Followed by Lenalidomide Maintenance in Patients With Multiple Myeloma: A Phase II Study by the Intergroupe Francophone du My\u00e9lome","volume":"32","author":"Roussel","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): A randomised, open-label, phase 3 study","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/j.clml.2019.09.004","article-title":"Daratumumab Plus Bortezomib, Thalidomide, and Dexamethasone (D-VTd) in Transplant-eligible Newly Diagnosed Multiple Myeloma (NDMM): Subgroup Analysis of High-risk Patients (Pts) in CASSIOPEIA","volume":"19","author":"Sonneveld","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41408-024-01088-6","article-title":"Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: Final analysis of clinically relevant subgroups in GRIFFIN","volume":"14","author":"Chari","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1056\/NEJMoa2312054","article-title":"Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"390","author":"Sonneveld","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dimopoulos, M.A., Sonneveld, P., Rodr\u00edguez-Otero, P., Quach, H., Ho, P.J., Beksac, M., Hulin, C., Antonioli, E., Leleu, X., and Mangiacavalli, S. (April, January 30). (DARA)\/bortezomib\/lenalidomide\/dexamethasone (D-VRd) with D-R maintenance (maint) in transplant-eligible (TE) newly diagnosed myeloma (NDMM): Analysis of PERSEUS based on cytogenetic risk. Proceedings of the EBMT 51st Annual Meeting, Florence, Italy.","DOI":"10.1016\/S2152-2650(24)01889-5"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1182\/blood.2023023597","article-title":"Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma","volume":"143","author":"Touzeau","year":"2024","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1182\/blood-2023-177546","article-title":"Results of the Phase III Randomized Iskia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone Vs Carfilzomib-Lenalidomide-Dexamethasone As Pre-Transplant Induction and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients","volume":"142","author":"Gay","year":"2023","journal-title":"Blood"},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1182\/blood.V122.21.767.767","article-title":"Double Vs Single Autologous Stem Cell Transplantation After Bortezomib-Based Induction Regimens for Multiple Myeloma: An Integrated Analysis of Patient-Level Data from Phase European III Studies","volume":"122","author":"Cavo","year":"2013","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1016\/j.bbmt.2019.07.004","article-title":"Tandem Autologous Stem Cell Transplantation Improves Outcomes in Newly Diagnosed Multiple Myeloma with Extramedullary Disease and High-Risk Cytogenetics: A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation","volume":"25","author":"Gagelmann","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1182\/blood.V128.22.991.991","article-title":"Upfront Single Versus Double Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma: An Intergroup, Multicenter, Phase III Study of the European Myeloma Network (EMN02\/HO95 MM Trial)","volume":"128","author":"Cavo","year":"2016","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41408-019-0205-9","article-title":"Current status of autologous stem cell transplantation for multiple myeloma","volume":"9","author":"Bazarbachi","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8506","DOI":"10.1200\/JCO.2020.38.15_suppl.8506","article-title":"Long-term follow-up of BMT CTN 0702 (STaMINA) of postautologous hematopoietic cell transplantation (autoHCT) strategies in the upfront treatment of multiple myeloma (MM)","volume":"38","author":"Hari","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S1470-2045(20)30756-7","article-title":"Treatment of relapsed and refractory multiple myeloma: Recommendations from the International Myeloma Working Group","volume":"22","author":"Moreau","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e456","DOI":"10.1016\/S2352-3026(20)30099-5","article-title":"Autologous haematopoietic stem-cell transplantation versus bortezomib\u2013melphalan\u2013prednisone, with or without bortezomib\u2013lenalidomide\u2013dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02\/HO95): A multicentre, randomised, open-label, phase 3 study","volume":"7","author":"Cavo","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1200\/JCO.21.01045","article-title":"Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma","volume":"39","author":"Sonneveld","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/14737140.2018.1490181","article-title":"Maintenance and continuous therapy for multiple myeloma","volume":"18","author":"Richardson","year":"2018","journal-title":"Expert. Rev. Anticancer. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1200\/JCO.2017.72.6679","article-title":"Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis","volume":"35","author":"McCarthy","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/leu.2013.335","article-title":"Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients","volume":"28","author":"Nooka","year":"2013","journal-title":"Leukemia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/leu.2017.211","article-title":"Bortezomib before and after high-dose therapy in myeloma: Long-term results from the phase III HOVON-65\/GMMG-HD4 trial","volume":"32","author":"Goldschmidt","year":"2018","journal-title":"Leukemia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/S1470-2045(21)00428-9","article-title":"Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): An open-label, randomised, phase 3 trial","volume":"22","author":"Moreau","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0140-6736(18)33003-4","article-title":"Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): A double-blind, randomised, placebo-controlled phase 3 trial","volume":"393","author":"Dimopoulos","year":"2019","journal-title":"Lancet"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1080\/14796694.2024.2394323","article-title":"A plain language summary of the PERSEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for treating newly diagnosed multiple myeloma","volume":"20","author":"Sonneveld","year":"2024","journal-title":"Futur. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/s41375-018-0098-9","article-title":"Front-line therapies for elderly patients with transplant-ineligible multiple myeloma and high-risk cytogenetics in the era of novel agents","volume":"32","author":"Facon","year":"2018","journal-title":"Leukemia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1056\/NEJMoa0801479","article-title":"VISTA trial investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma","volume":"359","author":"Schlag","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1182\/blood-2017-07-795047","article-title":"Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma","volume":"131","author":"Facon","year":"2018","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0140-6736(16)31594-X","article-title":"Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): A randomised, open-label, phase 3 trial","volume":"389","author":"Durie","year":"2017","journal-title":"Lancet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1016\/S2352-3026(20)30354-9","article-title":"Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): Primary analysis of a randomised, phase 2 trial","volume":"8","author":"Usmani","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1182\/blood-2019-123426","article-title":"Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant: Updated Analysis of Maia","volume":"134","author":"Bahlis","year":"2019","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7297","DOI":"10.1182\/blood-2022-163494","article-title":"Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Transplant-Ineligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Clinical Assessment of Key Subgroups of the Phase 3 Maia Study","volume":"140","author":"Moreau","year":"2022","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa1714678","article-title":"Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma","volume":"378","author":"Mateos","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_86","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","volume":"6","author":"Giri","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3324\/haematol.2019.243428","article-title":"Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: A pooled analysis of two studies","volume":"106","author":"Mina","year":"2020","journal-title":"Haematologica"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa2400712","article-title":"Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"391","author":"Facon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1038\/s41591-024-03485-7","article-title":"Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: The randomized phase 3 CEPHEUS trial","volume":"31","author":"Usmani","year":"2025","journal-title":"Nat. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1200\/JCO.21.01987","article-title":"In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present from Diagnosis in Tiny, Undetectable Subclonal Populations","volume":"41","author":"Lannes","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.3324\/haematol.2018.194282","article-title":"Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: Updated analysis of POLLUX","volume":"103","author":"Dimopoulos","year":"2018","journal-title":"Haematologica"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1182\/blood-2016-03-707596","article-title":"Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma","volume":"128","author":"Fonseca","year":"2016","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1182\/blood-2017-06-791228","article-title":"Ixazomib significantly prolongs progression-free survival in high-risk relapsed\/refractory myeloma patients","volume":"130","author":"Bahlis","year":"2017","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1002\/cncr.31680","article-title":"Elotuzumab plus lenalidomide and dexamethasone in relapsed\/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial","volume":"124","author":"Dimopoulos","year":"2018","journal-title":"Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1056\/NEJMoa1411321","article-title":"Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma","volume":"372","author":"Stewart","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/S0140-6736(21)00592-4","article-title":"Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): A multicentre, open-label, randomised phase 3 trial","volume":"397","author":"Moreau","year":"2021","journal-title":"Lancet"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S1470-2045(21)00128-5","article-title":"Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): An open-label, randomised, phase 3 trial","volume":"22","author":"Dimopoulos","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/ejh.13835","article-title":"Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis","volume":"109","author":"Spicka","year":"2022","journal-title":"Eur. J. Haematol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1038\/s41375-020-0813-1","article-title":"Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment","volume":"34","author":"Siegel","year":"2020","journal-title":"Leukemia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"S571","DOI":"10.1016\/S2152-2650(24)01705-1","article-title":"MM-557 DREAMM-7 Update: Subgroup Analyses From a Phase 3 Trial of Belantamab Mafodotin (Belamaf) + Bortezomib and Dexamethasone (BVd) vs Daratumumab, Bortezomib, and Dexamethasone (DVd) in Relapsed\/Refractory Multiple Myeloma (RRMM)","volume":"24","author":"Victoria","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/ajh.26261","article-title":"Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk","volume":"96","author":"Richard","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"De Novellis, D., Fontana, R., Giudice, V., Serio, B., and Selleri, C. (2022). Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010645"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa2203478","article-title":"Teclistamab in Relapsed or Refractory Multiple Myeloma","volume":"387","author":"Moreau","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e20017","DOI":"10.1200\/JCO.2023.41.16_suppl.e20017","article-title":"Efficacy and safety of elranatamab in patients with high-risk relapsed\/refractory multiple myeloma (RRMM): A subgroup analysis from MagnetisMM-3","volume":"41","author":"Larson","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-Cell\u2013Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2147\/CMAR.S372237","article-title":"Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody","volume":"15","author":"Pan","year":"2023","journal-title":"Cancer Manag. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1182\/blood-2022-159711","article-title":"Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study","volume":"140","author":"Searle","year":"2022","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"TPS8074","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS8074","article-title":"MagnetisMM-5: An open-label, multicenter, randomized phase 3 study of elranatamab as monotherapy and in combination with daratumumab in patients with relapsed\/refractory multiple myeloma","volume":"40","author":"Grosicki","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e15362d7","DOI":"10.1097\/01.HS9.0000967672.15362.d7","article-title":"S190: First results from the redirectt-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting bcma and gprc5d in patients (pts) with relapsed\/refractory multiple myeloma (rrmm)","volume":"7","author":"Mateos","year":"2023","journal-title":"HemaSphere"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e6102468","DOI":"10.1097\/01.HS9.0000967720.61024.68","article-title":"S202: Cartitude-1 Final Results: Phase 1b\/2 Study of Ciltacabtagene Autoleucel in Heavily Pretreated Patients with Relapsed\/Refractory Multiple Myeloma","volume":"7","author":"Munshi","year":"2023","journal-title":"HemaSphere"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1200\/JCO.22.00842","article-title":"Ciltacabtagene Autoleucel, an Anti\u2013B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed\/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up","volume":"41","author":"Martin","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"S572","DOI":"10.1016\/S2152-2650(24)01708-7","article-title":"MM-567 Ciltacabtagene Autoleucel vs Standard of Care in Lenalidomide-Refractory Multiple Myeloma: Phase 3 CARTITUDE-4 Subgroup Analysis by Cytogenetic Risk","volume":"24","author":"Mina","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, H., Lan, H., Wu, J., and Xiao, Y. (2023). CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1101495"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/11\/776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:40:00Z","timestamp":1760031600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/11\/776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,25]]},"references-count":114,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cells14110776"],"URL":"https:\/\/doi.org\/10.3390\/cells14110776","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,25]]}}}