{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:27:47Z","timestamp":1791613667216,"version":"4.3.4"},"reference-count":114,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma is biologically and clinically a complex and heterogeneous disease which develops late in life, with the median age at the time of initial diagnosis being 66 years. In 1975, Durie and Salmon developed the first broadly adopted staging system in multiple myeloma, and in the ensuing decades, the risk stratification tools have improved and now incorporate different parameters to better predict the prognosis and to guide the treatment decisions. The International Staging System (ISS) was initially developed in 2005, revised in 2015 (R-ISS), and again in 2022 (R2-ISS). Tremendous progress has been achieved in multiple myeloma therapy over the past 25 years with the approval of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, resulting in a major paradigm shift. The dysfunction of the innate and adaptive immune system, especially in the T cell repertoire, represents a hallmark of multiple myeloma evolution over time, supporting the need for additional therapeutic approaches to activate the host\u2019s immune system and to overcome the immunosuppressive tumor microenvironment. Novel T cell-directed therapies include chimeric antigen receptor (CAR) T cell therapies and bispecific antibodies that leverage the immune system\u2019s T cells to recognize and attack the tumor cells. Second-generation anti-BCMA CAR T cell therapies and bispecific antibodies that bind the tumor antigen BCMA or GPRC5D onto myeloma cells and CD3 on the T cell\u2019s surface are currently available for the treatment of relapsed\/refractory multiple myeloma. Despite impressive results obtained with currently approved treatments, multiple myeloma remains incurable, and almost all patients eventually relapse. Moreover, patients with extramedullary disease and plasma cell leukemia represent an unmet medical need that require additional strategies to improve the outcome. In this review, we provide an overview of the evolution of risk stratification and the treatment of multiple myeloma.<\/jats:p>","DOI":"10.3390\/cancers17030525","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T05:50:36Z","timestamp":1738734636000},"page":"525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Evolving Landscape in Multiple Myeloma: From Risk Stratification to T Cell-Directed Advanced Therapies"],"prefix":"10.3390","volume":"17","author":[{"given":"Carmen","family":"Besliu","sequence":"first","affiliation":[{"name":"Fortrea Inc., 8 Moore Drive, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Daniela","family":"Tanase","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute Bucharest, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionela","family":"Rotaru","sequence":"additional","affiliation":[{"name":"Department of Hematology, Municipal Hospital Craiova, 010024 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Fortrea Inc., 8 Moore Drive, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vidal","sequence":"additional","affiliation":[{"name":"Fortrea Inc., 8 Moore Drive, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Poelman","sequence":"additional","affiliation":[{"name":"Fortrea Inc., 8 Moore Drive, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-1648","authenticated-orcid":false,"given":"Manel","family":"Juan","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-9255","authenticated-orcid":false,"given":"Carlos Fern\u00e1ndez","family":"de Larrea","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-3309","authenticated-orcid":false,"given":"Kamal S.","family":"Saini","sequence":"additional","affiliation":[{"name":"Fortrea Inc., 8 Moore Drive, Durham, NC 27709, USA"},{"name":"Addenbrooke\u2019s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/j.seminoncol.2016.11.004","article-title":"Multiple Myeloma Epidemiology and Survival: A Unique Malignancy","volume":"43","author":"Kazandjian","year":"2016","journal-title":"Semin. Oncol."},{"key":"ref_2","unstructured":"(2024, September 24). Global Cancer Observatory, Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/cancers\/35-multiple-myeloma-fact-sheet.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.5694\/mja2.52366","article-title":"Multiple myeloma incidence, mortality, and prevalence estimates and projections, Australia, 1982\u20132043: A statistical modelling study","volume":"221","author":"Luo","year":"2024","journal-title":"Med. J. Aust."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4065\/78.1.21","article-title":"Review of 1027 patients with newly diagnosed multiple myeloma","volume":"78","author":"Kyle","year":"2003","journal-title":"Mayo Clin. Proc."},{"key":"ref_5","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_6","unstructured":"FDA (2024, September 25). Approved Drugs Daratumumab (Darzalex), Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/daratumumab-darzalex."},{"key":"ref_7","unstructured":"FDA (2024, September 25). Approved Drugs Idecabtagene Vicleucel, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-idecabtagene-vicleucel-multiple-myeloma."},{"key":"ref_8","unstructured":"FDA (2024, September 25). Approved Drugs Teclistamab-Cqyv, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.3324\/haematol.2020.247015","article-title":"Multiple myeloma: The (r)evolution of current therapy and a glance into future","volume":"105","author":"Gulla","year":"2020","journal-title":"Haematologica"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S1470-2045(11)70143-7","article-title":"Multiple myeloma and the road to personalised medicine","volume":"12","author":"Russell","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/ajh.26590","article-title":"Multiple myeloma: 2022 update on diagnosis, risk stratification, and management","volume":"97","author":"Rajkumar","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U","article-title":"A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival","volume":"36","author":"Durie","year":"1975","journal-title":"Cancer"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/leu.2009.61","article-title":"Is the International Staging System superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant","volume":"23","author":"Hari","year":"2009","journal-title":"Leukemia"},{"key":"ref_16","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_17","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_18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0025-6196(11)61029-X","article-title":"Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): Consensus statement","volume":"82","author":"Dispenzieri","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.mayocp.2013.01.019","article-title":"Management of newly diagnosed symptomatic multiple myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013","volume":"88","author":"Mikhael","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e420064a","DOI":"10.1097\/01.HS9.0000970728.42006.4a","article-title":"P956: Validation of the second revision of the international staging system (r2-iss) for overall survival in multiple myeloma in a real world cohort: An analysis by the balkan myeloma study group (bmsg)","volume":"7","author":"Kastritis","year":"2023","journal-title":"HemaSphere"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1200\/JCO.23.01277","article-title":"Genomic Classification and Individualized Prognosis in Multiple Myeloma","volume":"42","author":"Maura","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1200\/EDBK_320105","article-title":"How to Treat High-Risk Myeloma at Diagnosis and Relapse","volume":"41","author":"Caro","year":"2021","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13045-024-01555-4","article-title":"Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel","volume":"17","author":"Zanwar","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1182\/blood-2014-12-615187","article-title":"Geriatric assessment predicts survival and toxicities in elderly myeloma patients: An International Myeloma Working Group report","volume":"125","author":"Palumbo","year":"2015","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/s41375-019-0595-5","article-title":"The relative importance of factors predicting outcome for myeloma patients at different ages: Results from 3894 patients in the Myeloma XI trial","volume":"34","author":"Pawlyn","year":"2020","journal-title":"Leukemia"},{"key":"ref_26","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_27","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_28","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1056\/NEJMoa2303379","article-title":"Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma","volume":"389","author":"Dhakal","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.3324\/haematol.11534","article-title":"Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma","volume":"92","author":"Liu","year":"2007","journal-title":"Haematologica"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e328","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":"ref_32","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.1182\/bloodadvances.2020002827","article-title":"A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma","volume":"4","author":"Munshi","year":"2020","journal-title":"Blood Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1182\/blood.2021011101","article-title":"Prognostic value of minimal residual disease negativity in myeloma: Combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA","volume":"139","author":"Cavo","year":"2022","journal-title":"Blood"},{"key":"ref_34","unstructured":"FDA (2024, September 25). Final Summary Minutes of the Oncologic Drugs Advisory Committee Meeting, Available online: https:\/\/www.fda.gov\/media\/180108\/download."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/095952874402700129","article-title":"Remarks on the Pathology of Mollities Ossium. With Cases","volume":"27","author":"Solly","year":"1844","journal-title":"J. R. Soc. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1177\/095952875003300113","article-title":"Case of Mollities and Fragilitas Ossium, accompanied with urine strongly charged with animal matter","volume":"33","author":"Macintyre","year":"1850","journal-title":"Medico-Chir. Trans."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S0140-6736(47)90375-9","article-title":"Urethane and stilbamidine in multiple myeloma report on two cases","volume":"2","author":"Alwall","year":"1947","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/j.1749-6632.1958.tb42675.x","article-title":"Clinical experiences with sarcolysin in neoplastic diseases","volume":"68","author":"Blokhin","year":"1958","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1001\/jama.1969.03160090040009","article-title":"Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens","volume":"208","author":"Alexanian","year":"1969","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Myeloma Trialists\u2019 Collaborative Group (1998). Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: An overview of 6,633 patients from 27 randomized trials. J. Clin. Oncol., 16, 3832\u20133842.","DOI":"10.1200\/JCO.1998.16.12.3832"},{"key":"ref_41","first-page":"318","article-title":"Chemotherapy of previously untreated multiple myeloma patients: An analysis of recent treatment results","volume":"13","author":"Sporn","year":"1986","journal-title":"Semin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1056\/NEJMoa022340","article-title":"Medical Research Council Adult Leukaemia Working Party High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma","volume":"348","author":"Child","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S0140-6736(83)90739-0","article-title":"High-dose intravenous melphalan for plasma-cell leukaemia and myeloma","volume":"2","author":"McElwain","year":"1983","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1056\/NEJM199607113350204","article-title":"A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Fran\u00e7ais du My\u00e9lome","volume":"335","author":"Attal","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1182\/blood.V126.23.391.391","article-title":"Autologous Transplantation for Multiple Myeloma in the Era of New Drugs: A Phase III Study of the Intergroupe Francophone Du Myelome (IFM\/DFCI 2009 Trial)","volume":"126","author":"Attal","year":"2015","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1182\/blood-2020-134538","article-title":"Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Analysis of the IFM 2009 Trial","volume":"136","author":"Perrot","year":"2020","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1056\/NEJMoa2204925","article-title":"Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma","volume":"387","author":"Richardson","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1038\/s41591-024-03050-2","article-title":"Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: The randomized phase 3 BENEFIT trial","volume":"30","author":"Leleu","year":"2024","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"867","DOI":"10.4065\/79.7.867","article-title":"Clinical course of patients with relapsed multiple myeloma","volume":"79","author":"Kumar","year":"2004","journal-title":"Mayo Clin. Proc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/s41375-022-01531-2","article-title":"LocoMMotion: A prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and\/or refractory multiple myeloma","volume":"36","author":"Mateos","year":"2022","journal-title":"Leukemia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1038\/leu.2016.84","article-title":"Multiple myeloma causes clonal T-cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade","volume":"30","author":"Suen","year":"2016","journal-title":"Leukemia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1158\/1078-0432.CCR-19-2111","article-title":"How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma","volume":"26","author":"Cohen","year":"2020","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/j.1365-2141.2008.07530.x","article-title":"CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(\u2212)CD8(\u2212)alphabetaTCR(+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden","volume":"144","author":"Feyler","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e127807","DOI":"10.1172\/jci.insight.127807","article-title":"Early alterations in stem-like\/resident T cells, innate and myeloid cells in the bone marrow in preneoplastic gammopathy","volume":"5","author":"Bailur","year":"2019","journal-title":"JCI Insight"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.tcb.2020.06.003","article-title":"The Roles of CD8+ T Cell Subsets in Antitumor Immunity","volume":"30","author":"Ohashi","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s10753-014-9980-4","article-title":"The alteration and clinical significance of Th1\/Th2\/Th17\/Treg cells in patients with multiple myeloma","volume":"38","author":"Feng","year":"2015","journal-title":"Inflammation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrc2355","article-title":"Adoptive cell transfer: A clinical path to effective cancer immunotherapy","volume":"8","author":"Rosenberg","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa1215134","article-title":"Chimeric antigen receptor-modified T cells for acute lymphoid leukemia","volume":"368","author":"Grupp","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zhang, C., Liu, J., Zhong, J.F., and Zhang, X. (2017). Engineering CAR-T cells. Biomark. Res., 5.","DOI":"10.1186\/s40364-017-0102-y"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1097\/BS9.0000000000000173","article-title":"CAR-T cell therapy: Where are we now, and where are we heading?","volume":"5","author":"Wang","year":"2023","journal-title":"Blood Sci. Baltim. Md"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/imr.12125","article-title":"Of CARs and TRUCKs: Chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma","volume":"257","author":"Chmielewski","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Mishra, A.K., Gupta, A., Dagar, G., Das, D., Chakraborty, A., Haque, S., Prasad, C.P., Singh, A., Bhat, A.A., and Macha, M.A. (2023). CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond. Vaccines, 11.","DOI":"10.3390\/vaccines11111721"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0140-6736(21)00933-8","article-title":"Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b\/2 open-label study","volume":"398","author":"Berdeja","year":"2021","journal-title":"Lancet"},{"key":"ref_65","unstructured":"FDA (2024, September 25). Approved Drug Ciltacabtagene Autoleucel, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-ciltacabtagene-autoleucel-relapsed-or-refractory-multiple-myeloma."},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2217\/fon-2021-1090","article-title":"Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma","volume":"18","author":"Anderson","year":"2022","journal-title":"Future Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1200\/JCO.22.00842","article-title":"Ciltacabtagene Autoleucel, an Anti-B-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_69","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1056\/NEJMoa2213614","article-title":"Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma","volume":"388","author":"Ailawadhi","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1182\/blood.2024024582","article-title":"Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: Updated KarMMa-3 analyses","volume":"144","author":"Ailawadhi","year":"2024","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1182\/blood.2020005288","article-title":"Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: The GRIFFIN trial","volume":"136","author":"Voorhees","year":"2020","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fonseca, R., Usmani, S.Z., Mehra, M., Slavcev, M., He, J., Cote, S., Lam, A., Ukropec, J., Maiese, E.M., and Nair, S. (2020). Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07503-y"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1158\/2643-3230.BCD-22-0074","article-title":"Anti-BCMA\/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy","volume":"4","author":"Garfall","year":"2023","journal-title":"Blood Cancer Discov."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"101628","DOI":"10.1016\/j.jgo.2023.101628","article-title":"Safety and efficacy of anti-BCMA CAR-T cell therapy in older adults with multiple myeloma: A systematic review and meta-analysis","volume":"15","author":"Akhtar","year":"2024","journal-title":"J. Geriatr. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1182\/blood-2023-181331","article-title":"Outcomes of BCMA-Directed Chimeric Antigen Receptor T-Cell (CART) Therapy in Patients with Relapse-Refractory Multiple Myeloma with Extramedullary Disease","volume":"142","author":"Dima","year":"2023","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1200\/JCO.22.01365","article-title":"Idecabtagene Vicleucel for Relapsed\/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium","volume":"41","author":"Hansen","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8012","DOI":"10.1200\/JCO.2023.41.16_suppl.8012","article-title":"Safety and efficacy of standard of care (SOC) ciltacabtagene autoleucel (Cilta-cel) for relapsed\/refractory multiple myeloma (RRMM)","volume":"41","author":"Hansen","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6937","DOI":"10.1182\/blood-2023-188090","article-title":"Incidence of Parkinsonism as a Complication of Anti-BCMA CAR-T Cell Therapy in Multiple Myeloma","volume":"142","author":"Singh","year":"2023","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3978","DOI":"10.1200\/JCO.21.01992","article-title":"Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline","volume":"39","author":"Santomasso","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e374","DOI":"10.1016\/S1470-2045(24)00094-9","article-title":"Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: A report from the International Myeloma Working Group Immunotherapy Committee","volume":"25","author":"Lin","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1016\/j.clml.2024.01.014","article-title":"Optimizing the CAR T-Cell Therapy Experience in Multiple Myeloma: Clinical Pearls From an Expert Roundtable","volume":"24","author":"Ailawadhi","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.jcyt.2022.05.003","article-title":"Leukapheresis guidance and best practices for optimal chimeric antigen receptor T-cell manufacturing","volume":"24","author":"Qayed","year":"2022","journal-title":"Cytotherapy"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Mitra, A., Barua, A., Huang, L., Ganguly, S., Feng, Q., and He, B. (2023). From bench to bedside: The history and progress of CAR T cell therapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1188049"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2147\/BLCTT.S327016","article-title":"CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges","volume":"12","author":"Rendo","year":"2022","journal-title":"Blood Lymphat. Cancer Targets Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41571-022-00607-3","article-title":"Preparing for CAR T cell therapy: Patient selection, bridging therapies and lymphodepletion","volume":"19","author":"Amini","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_87","unstructured":"(2024, September 25). Product Information Abecma. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/abecma-epar-product-information_en.pdf."},{"key":"ref_88","unstructured":"(2024, September 25). Product Information Carvykti. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/carvykti-epar-product-information_en.pdf."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.jtct.2022.06.021","article-title":"Real-World Experience and Optimization of Outpatient Chimeric Antigen Receptor T Cell Therapy","volume":"28","author":"McGann","year":"2022","journal-title":"Transplant. Cell. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jtct.2023.11.008","article-title":"Chimeric Antigen Receptor T-Cell Therapy in the Outpatient Setting: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy","volume":"30","author":"Oluwole","year":"2024","journal-title":"Transplant. Cell. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1182\/blood-2021-146210","article-title":"Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed By Ciltacabtagene Autoleucel Versus Vrd Followed By Lenalidomide and Dexamethasone (Rd) Maintenance in Patients with Newly Diagnosed Multiple Myeloma Not Intended for Transplant: A Randomized, Phase 3 Study (CARTITUDE-5)","volume":"138","author":"Dytfeld","year":"2021","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/01.HS9.0000936220.68605.8b","article-title":"P23 Emagine\/cartitude-6: A randomized phase 3 study of dvrd followed by ciltacabtagene autoleucel versus dvrd followed by autologous stem cell transplant in transplant-eligible patients with newly diagnosed multiple myeloma","volume":"7","author":"Broijl","year":"2023","journal-title":"HemaSphere"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1182\/blood-2020-139009","article-title":"KarMMa-4: Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T-Cell Therapy, in High-Risk Newly Diagnosed Multiple Myeloma","volume":"136","author":"Usmani","year":"2020","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Miller, K., Hashmi, H., and Rajeeve, S. (2024). Beyond BCMA: The next wave of CAR T cell therapy in multiple myeloma. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1398902"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1056\/NEJMoa2209900","article-title":"GPRC5D-Targeted CAR T Cells for Myeloma","volume":"387","author":"Mailankody","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1158\/2643-3230.BCD-20-0020","article-title":"Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape-Driven Relapse in Multiple Myeloma","volume":"1","author":"Staehr","year":"2020","journal-title":"Blood Cancer Discov."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Alabanza, L.M., Xiong, Y., Vu, B., Webster, B., Wu, D., Hu, P., Zhu, Z., Dropulic, B., Dash, P., and Schneider, D. (2022). Armored BCMA CAR T Cells Eliminate Multiple Myeloma and Are Resistant to the Suppressive Effects of TGF-\u03b2. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.832645"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lonez, C., and Breman, E. (2024). Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met?. Cells, 13.","DOI":"10.3390\/cells13020146"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41591-022-02182-7","article-title":"Allogeneic BCMA-targeting CAR T cells in relapsed\/refractory multiple myeloma: Phase 1 UNIVERSAL trial interim results","volume":"29","author":"Mailankody","year":"2023","journal-title":"Nat. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/jha2.729","article-title":"T-cell redirecting bispecific antibodies in multiple myeloma: Current landscape and future directions","volume":"4","year":"2023","journal-title":"EJHaem"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Cho, S.-F., Yeh, T.-J., Anderson, K.C., and Tai, Y.-T. (2022). Bispecific antibodies in multiple myeloma treatment: A journey in progress. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1032775"},{"key":"ref_102","unstructured":"(2024, September 25). Product Information Talvey, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761342s000lbl.pdf."},{"key":"ref_103","unstructured":"(2024, September 25). Product Information Tecvayli, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761291s000lbl.pdf."},{"key":"ref_104","unstructured":"(2024, September 25). Product Information Elrexfio, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761345s000lbl.pdf."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1038\/s41591-023-02528-9","article-title":"Elranatamab in relapsed or refractory multiple myeloma: Phase 2 MagnetisMM-3 trial results","volume":"29","author":"Lesokhin","year":"2023","journal-title":"Nat. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1002\/hem3.136","article-title":"Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM-3 study","volume":"8","author":"Tomasson","year":"2024","journal-title":"HemaSphere"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e5955094","DOI":"10.1097\/01.HS9.0000967676.59550.94","article-title":"S191: Pivotal phase 2 monumental-1 results of talquetamab (tal), a gprc5dxcd3 bispecific antibody (bsab), for relapsed\/refractory multiple myeloma (rrmm)","volume":"7","author":"Touzeau","year":"2023","journal-title":"HemaSphere"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"S548","DOI":"10.1016\/S2152-2650(24)01666-5","article-title":"MM-336 Long-Term Follow-Up from the Phase 1\/2 MajesTEC-1 Trial of Teclistamab in Patients With Relapsed\/Refractory Multiple Myeloma (RRMM)","volume":"24","author":"Garfall","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1016\/S1470-2045(23)00159-6","article-title":"Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: A consensus report of the European Myeloma Network","volume":"24","author":"Ludwig","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41408-023-00966-9","article-title":"GPRC5D as a novel target for the treatment of multiple myeloma: A narrative review","volume":"14","author":"Pillarisetti","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1182\/blood-2021-147983","article-title":"Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed\/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study","volume":"138","author":"Trudel","year":"2021","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"10148","DOI":"10.1182\/blood-2022-160173","article-title":"Krishnan MajesTEC-7: A Phase 3, Randomized Study of Teclistamab + Daratumumab + Lenalidomide (Tec-DR) Versus Daratumumab + Lenalidomide + Dexamethasone (DRd) in Patients with Newly Diagnosed Multiple Myeloma Who Are Either Ineligible or Not Intended for Autologous Stem Cell Transplant","volume":"140","author":"Amrita","year":"2022","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e4258276","DOI":"10.1097\/01.HS9.0000975288.42582.76","article-title":"PB2131: Magnetismm-7: An open-label, multicenter, randomized phase 3 study of elranatamab versus lenalidomide in post-transplant patients with newly diagnosed multiple myeloma","volume":"7","author":"Manteca","year":"2023","journal-title":"HemaSphere"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/525\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:26:58Z","timestamp":1760027218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":114,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cancers17030525"],"URL":"https:\/\/doi.org\/10.3390\/cancers17030525","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]}}}