{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:02Z","timestamp":1789016822681,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"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>Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed\/refractory MM (R\/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R\/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.<\/jats:p>","DOI":"10.3390\/cancers13112639","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T11:07:02Z","timestamp":1622113622000},"page":"2639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-419X","authenticated-orcid":false,"given":"Massimo","family":"Martino","sequence":"first","affiliation":[{"name":"Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo Antonio","family":"Canale","sequence":"additional","affiliation":[{"name":"Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Alati","sequence":"additional","affiliation":[{"name":"Hematology Unit, Hemato-Oncology and Radiotherapy Department, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda Donatella","family":"Vincelli","sequence":"additional","affiliation":[{"name":"Hematology Unit, Hemato-Oncology and Radiotherapy Department, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Moscato","sequence":"additional","affiliation":[{"name":"Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetana","family":"Porto","sequence":"additional","affiliation":[{"name":"Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Loteta","sequence":"additional","affiliation":[{"name":"Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Naso","sequence":"additional","affiliation":[{"name":"Stem Cell Transplant and Cellular Therapies Unit, Hemato-Oncology and Radiotherapy Department, Grande OspedaleMetropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89124 Reggio Calabria, RC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-5743","authenticated-orcid":false,"given":"Massimiliano","family":"Mazza","sequence":"additional","affiliation":[{"name":"Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ghelli Luserna di Ror\u00e0","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6954-969X","authenticated-orcid":false,"given":"Giorgia","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Ronconi","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Ceccolini","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Musuraca","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1025-4210","authenticated-orcid":false,"given":"Giovanni","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-5436","authenticated-orcid":false,"given":"Claudio","family":"Cerchione","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-020-00359-2","article-title":"Multiple myeloma current treatment algorithms","volume":"10","author":"Rajkumar","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.6004\/jnccn.2020.0057","article-title":"Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology","volume":"18","author":"Kumar","year":"2020","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bonello, F., Grasso, M., D\u2019Agostino, M., Celeghini, I., Castellino, A., Boccadoro, M., and Bringhen, S. (2020). The Role of Monoclonal Antibodies in the First-Line Treatment of Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma. Pharmaceuticals, 14.","DOI":"10.3390\/ph14010020"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/bjh.17071","article-title":"Daratumumab monotherapy for relapsed\/refractory multiple myeloma, focussed on clinical trial-unfit patients and subsequent therapy","volume":"193","author":"Park","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Richter, J., and Thibaud, S. (2020). Anti-body building: The exercise of advancing immune based myeloma therapies. Blood Rev., 100789.","DOI":"10.1016\/j.blre.2020.100789"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zamagni, Z., Tacchetti, T., Deias, D., and Patriarca, P. (2020). The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120451"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mor\u00e8, S., Petrucci, M.T., Corvatta, L., Fazio, F., Offidani, M., and Olivieri, A. (2020). Monoclonal Antibodies: Leading Actors in the Relapsed\/Refractory Multiple Myeloma Treatment. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120426"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103211","DOI":"10.1016\/j.critrevonc.2020.103211","article-title":"Daratumumab-based induction therapy for multiple myeloma: A systematic review and meta-analysis","volume":"159","author":"Chong","year":"2021","journal-title":"Crit. Rev. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/17474086.2021.1858790","article-title":"A comprehensive overview of daratumumab and carfilzomib and the recently approved daratumumab, carfilzomib and dexamethasone regimen in relapsed\/refractory multiple myeloma","volume":"14","author":"Richard","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41408-020-00357-4","article-title":"Elotuzumab, lenalidomide, and dexamethasone in RRMM: Final overall survival results from the phase 3 randomized ELOQUENT-2 study","volume":"10","author":"Dimopoulos","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1080\/14712598.2021.1841747","article-title":"Isatuximab for the treatment of relapsed\/refractory multiple myeloma","volume":"20","author":"Richardson","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_12","first-page":"1","article-title":"Antibody-drug conjugates for multiple myeloma","volume":"12","author":"McMillan","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.2217\/fon-2020-0521","article-title":"Belantamab mafodotin in the treatment of relapsed or refractory multiple myeloma","volume":"16","author":"Sheikh","year":"2020","journal-title":"Future Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13045-020-00962-7","article-title":"BCMA-targeted immunotherapy for multiple myeloma","volume":"13","author":"Yu","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1158\/1078-0432.CCR-12-2422","article-title":"B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple mye- loma","volume":"19","author":"Carpenter","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.18632\/oncotarget.27792","article-title":"T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma","volume":"11","author":"Verkleij","year":"2020","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Palma, B., Marchica, V., Catarozzo, M.T., Giuliani, N., and Accardi, F. (2020). Monoclonal and Bispecific Anti-BCMA Antibodies in Multiple Myeloma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9093022"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1182\/hematology.2020000111","article-title":"Future of CAR T cells in multiple myeloma","volume":"2020","author":"Wudhikarn","year":"2020","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13045-020-01001-1","article-title":"Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma","volume":"13","author":"Roex","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Otero, P., Pr\u00f3sper, F., Alfonso, A., Paiva, B., and San Miguel, J.F. (2020). CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. J. Clin. Med., 9.","DOI":"10.3390\/jcm9113577"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104193","DOI":"10.1016\/j.cellimm.2020.104193","article-title":"Regulatory T cell therapy: Current and future design perspectives","volume":"356","author":"Rana","year":"2020","journal-title":"Cell Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2147\/ITT.S240886","article-title":"Immunotherapeutic and Targeted Approaches in Multiple Myeloma","volume":"9","author":"Nadeem","year":"2020","journal-title":"Immunotargets Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients withmultiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8503","DOI":"10.1200\/JCO.2020.38.15_suppl.8503","article-title":"Idecabtagenevicleucel, a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma: Initial KarMMa results","volume":"38","author":"Munshi","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1182\/blood-2019-126660","article-title":"Updated Results from an Ongoing Phase 1 Clinical Study of bb21217 Anti-Bcma CAR T Cell Therapy","volume":"134","author":"Berdeja","year":"2019","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1182\/blood-2020-140410","article-title":"Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes","volume":"136","author":"Alsina","year":"2020","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8505","DOI":"10.1200\/JCO.2020.38.15_suppl.8505","article-title":"Update of CARTITUDE-1: A phase Ib\/II study of JNJ-4528, a B-cell maturation antigen-directed CAR-T-cell therapy, in relapsed\/refractory multiple myeloma","volume":"38","author":"Berdeja","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1182\/blood-2020-136307","article-title":"CARTITUDE-1: Phase 1b\/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen\u2013directed chimeric antigen receptor T cell therapy, in relapsed\/refractory multiple myeloma","volume":"136","author":"Madduri","year":"2020","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1182\/blood-2018-99-113548","article-title":"JCARH125, anti-BCMA CAR T-cell therapy for relapsed\/refractory multiple myeloma: Initial proof of concept results from a phase 1\/2 multicenter study (EVOLVE)","volume":"132","author":"Mailankody","year":"2018","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8504","DOI":"10.1200\/JCO.2020.38.15_suppl.8504","article-title":"Orvacabtageneautoleucel (orva-cel), a B-cell maturation antigen (BCMA)-directed CAR T cell therapy for patients (pts) with relapsed\/refractory multiple myeloma (RRMM): Update of the phase 1\/2 EVOLVE study (NCT03430011)","volume":"38","author":"Mailankody","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_31","first-page":"26","article-title":"Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated Results from Phase 1 CRB-401","volume":"136","author":"Lin","year":"2020","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1182\/blood-2017-01-725705","article-title":"How I manage the toxicities of myeloma drugs","volume":"129","author":"Delforge","year":"2017","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1182\/blood-2020-136665","article-title":"Secondary Quality-of-Life Domains in Patients with Relapsed and Refractory Multiple Myeloma Treated with the BCMA-Directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel; bb2121): Results from the Karmma Clinical Trial","volume":"136","author":"Shah","year":"2020","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1182\/blood-2019-124953","article-title":"Long-term follow-up of a phase I, first-in-human open-label study of LCAR-B38M, a structurally differentiated chimeric antigen receptor T cell therapy targeting B-cell maturation antigen, in patients with relapsed\/refractory multiple myeloma","volume":"134","author":"Wang","year":"2019","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1182\/blood-2019-121731","article-title":"Results from CARTITUDE-1: A Phase 1b\/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and\/or Refractory Multiple Myeloma (R\/R MM)","volume":"134","author":"Madduri","year":"2019","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41591-018-0010-1","article-title":"Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia","volume":"4","author":"Fraietta","year":"2018","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1182\/blood-2018-99-116953","article-title":"Initial Results from a Phase 1 Clinical Study of bb21217, a Next-Generation Anti Bcma CAR T Therapy","volume":"132","author":"Shah","year":"2018","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Alsina, M., Shah, N., Raje, N.S., Jagannath, S., Madduri, D., Kaufman, J.L., Siegel, D.S., and Munshi, N.C. (2020, January 5\u20138). Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes. Proceedings of the 62nd ASH Annual Meeting & Exposition, San Diego, CA, USA.","DOI":"10.1182\/blood-2020-140410"},{"key":"ref_39","first-page":"504","article-title":"T Cells Expressing Anti-B-Cell Maturation Antigen (BCMA) Chimeric Antigen Receptors with Antigen Recognition Domains Made up of Only Single Human Heavy Chain Variable Domains Specifically Recognize Bcma and Eradicate Tumors in Mice","volume":"130","author":"Lam","year":"2017","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1182\/blood-2020-138839","article-title":"Deep and Durable Remissions of Relapsed Multiple Myeloma on a First-in-Humans Clinical Trial of T Cells Expressing an Anti-B-Cell Maturation Antigen (BCMA) Chimeric Antigen Receptor (CAR) with a Fully-Human Heavy-Chain-Only Antigen Recognition Domain","volume":"136","author":"Mikkilineni","year":"2019","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1182\/blood-2019-126104","article-title":"Phase 1 Trial of the Safety and Efficacy of Fully Human Anti-Bcma CAR T Cells in Relapsed\/Refractory Multiple Myeloma","volume":"134","author":"Jie","year":"2019","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1182\/blood-2020-139802","article-title":"Results from Lummicar-2: A Phase 1b\/2 Study of Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT053) in Patients with Relapsed and\/or Refractory Multiple Myeloma","volume":"136","author":"Kumar","year":"2020","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s00262-018-2155-7","article-title":"Induction of a central memory and stem cell memory phenotype in functionally active CD4+ and CD8+ CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19+ acute lymphoblastic leukemia","volume":"67","author":"Blaeschke","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1126\/science.abb9847","article-title":"Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer","volume":"370","author":"Krishna","year":"2020","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"120","DOI":"10.21037\/atm.2017.02.28","article-title":"Human stem memory T cells (TSCM) as critical players in the long-term persistence of immune responses","volume":"5","author":"Morrot","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s13238-020-00707-9","article-title":"Memory T cells: Strategies for optimizing tumor immunotherapy","volume":"11","author":"Liu","year":"2020","journal-title":"Protein Cell"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Costello, C.L., Cohen, A.D., Patel, K.K., Ali, S.S., Berdeja, J.G., Shah, N., Ganguly, S., Kocoglu, M.H., Abedi, M., and Ostertag, E.M. (2020, January 5\u20138). Phase 1\/2 Study of the Safety and Response of P-BCMA-101 CAR-T Cells in Patients with Relapsed\/Refractory (r\/r) Multiple Myeloma (MM) (PRIME) with Novel Therapeutic Strategies. Proceedings of the 62nd ASH Annual Meeting and Exposition, San Diego, CA, USA.","DOI":"10.1182\/blood-2020-142695"},{"key":"ref_48","unstructured":"(2021, April 23). Clinical Trial \u201cEfficacy and Safety Study of bb2121 Versus Standard Triplet Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3)\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03651128."},{"key":"ref_49","unstructured":"(2021, April 23). Clinical Trial \u201cA Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4)\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04181827."},{"key":"ref_50","unstructured":"(2021, April 23). Clinical Trial \u201cA Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4) (KarMMa-4)\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04196491."},{"key":"ref_51","unstructured":"(2021, April 23). Clinical Trial \u201cA Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma (CARTITUDE-2)\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04133636."},{"key":"ref_52","unstructured":"(2021, April 23). Clinical Trial \u201cUp-front CART-BCMA with or without huCART19 in High-risk Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03549442."},{"key":"ref_53","unstructured":"(2021, April 23). Clinical Trial \u201cBCMA Chimeric Antigen Receptor Expressing T Cells Therapy for Relapsed\/Refractory Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03943472."},{"key":"ref_54","unstructured":"(2021, April 23). Clinical Trial \u201cBCMA Targeted CAR T Cells with or without Lenalidomide for the Treatment of Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03070327."},{"key":"ref_55","unstructured":"(2021, April 23). Clinical Trial \u201cBCMA-Specific CAR T-Cells Combined with a Gamma Secretase Inhibitor (JSMD194) to Treat Relapsed or Persistent Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03502577."},{"key":"ref_56","unstructured":"(2021, April 23). Clinical Trial \u201cCD4-specific CAR T Cells (CD4 CAR T Cells) for Relapsed\/Refractory T Cell Malignancies\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04162340."},{"key":"ref_57","unstructured":"(2021, April 23). Clinical Trial \u201cStudy to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03464916."},{"key":"ref_58","unstructured":"(2021, April 23). Clinical Trial \u201cStudy of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04097301."},{"key":"ref_59","unstructured":"(2021, April 23). Clinical Trial \u201cStudy of ATLCAR.CD138 Cells for Relapsed\/Refractory Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03672318."},{"key":"ref_60","unstructured":"(2021, April 23). Clinical Trial \u201cT-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03958656."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1182\/blood-2018-99-117964","article-title":"Tandom Autologous Transplantation and Combined Infusion of CD19 and Bcma-Specific Chimeric Antigen Receptor T Cells for High Risk MM: Initial Safety and Efficacy Report","volume":"132","author":"Shi","year":"2018","journal-title":"Blood"},{"key":"ref_62","first-page":"25","article-title":"Clinical Results of a Multicenter Study of the First-in-Human Dual BCMA and CD19 Targeted Novel Platform Fast CAR-T Cell Therapy for Patients with Relapsed\/Refractory Multiple Myeloma","volume":"136","author":"Jiang","year":"2020","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1182\/blood-2020-140641","article-title":"Universal: An Allogeneic First-in-Human Study of the Anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in Relapsed\/Refractory Multiple Myeloma","volume":"136","author":"Mailankody","year":"2020","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Cho, S.F., Lin, L., Xing, L., Li, Y., Yu, T., Anderson, K.C., and Tai, Y.T. (2020). BCMA-Targeting Therapy: Driving a New Era of Immunotherapy in Multiple Myeloma. Cancers, 12.","DOI":"10.3390\/cancers12061473"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"102975","DOI":"10.1016\/j.ebiom.2020.102975","article-title":"CAR-NK cells: A promising cellular immunotherapy for cancer","volume":"59","author":"Xie","year":"2020","journal-title":"EbioMedicine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.canlet.2019.11.033","article-title":"CAR-NK for tumor immunotherapy: Clinical transformation and future prospects","volume":"472","author":"Jiang","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_67","unstructured":"(2021, April 23). Clinical Trial \u201cClinical Research of Adoptive BCMA CAR-NK Cells on Relapse\/Refractory MM\u201d, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03940833."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1200\/JCO.2018.77.8084","article-title":"T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma","volume":"36","author":"Brudno","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1182\/blood-2018-99-117729","article-title":"Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma","volume":"132","author":"Green","year":"2018","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1172\/JCI126397","article-title":"B cell maturation antigen- specific CAR T cells are clinically active in multiple myeloma","volume":"129","author":"Cohen","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.3389\/fimmu.2019.01613","article-title":"Chimeric antigen receptor-modified T cell therapy in multiple myeloma: Beyond B cell maturation antigen","volume":"10","author":"Timmers","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eaau7746","DOI":"10.1126\/scitranslmed.aau7746","article-title":"GPRC5D is a target for the im- munotherapy of multiple myeloma with rationally designed CAR T cells","volume":"11","author":"Smith","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_73","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\u2013driven relapse in multiple mye- loma","volume":"1","author":"Staehr","year":"2020","journal-title":"Blood Cancer Discov."},{"key":"ref_74","unstructured":"(2021, April 23). Allo CAR T Therapy-The next revolution in cell therapy. Allogene Ther., Available online: https:\/\/www.allogene.com\/allocar-t-therapy."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/s41586-018-0326-5","article-title":"Reprogramming human T cell function and specificity with non-viral genome targeting","volume":"559","author":"Roth","year":"2018","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/nbt.2678","article-title":"Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy","volume":"31","author":"Themeli","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature22395","article-title":"Therapeutic T cell engineering","volume":"545","author":"Sadelain","year":"2017","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1182\/blood-2019-131373","article-title":"FT576: A novel multiplexed engineered off-the-shelf natural killer cell immunotherapy for the dual- targeting of CD38 and Bcma for the treatment of multiple myeloma","volume":"134","author":"Bjordahl","year":"2019","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1182\/blood-2017-06-793869","article-title":"Chimeric antigen receptor T-cell therapies for multiple myeloma","volume":"130","author":"Mikkilineni","year":"2017","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1200\/EDBK_175175","article-title":"Established and Novel Prognostic Biomarkers in Multiple Myeloma","volume":"37","author":"Bustoros","year":"2017","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/11\/2639\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:09:04Z","timestamp":1760162944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/11\/2639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,27]]},"references-count":80,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["cancers13112639"],"URL":"https:\/\/doi.org\/10.3390\/cancers13112639","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,27]]}}}