| Citation: |
QIAN Chenjing, HONG Mei, XIA Linghui. Advances in Emerging Therapies for Multiple Myeloma[J]. Cancer Research on Prevention and Treatment, 2023, 50(3): 321-325. DOI: 10.3971/j.issn.1000-8578.2023.22.0874
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Multiple myeloma (MM) is an incurable plasma cell malignancy with a typical course characterized by response to initial treatment and eventual resistance. Despite major advances in the clinical treatment of multiple myeloma driven by the introduction of new drugs (e.g., proteasome inhibitors and immunomodulators), MM remains incurable. Nevertheless, subsequent cycles of remission and relapse continue as long as new treatments are available to patients. With the development of many new treatments, the approval of 12 new drugs over the past 15 years, and the promising trend of clinical trials, the treatment landscape has dramatically changed and patient survival has improved. This article reviews the progress of new treatments for MM.
Competing interests: The authors declare that they have no competing interests.
| [1] |
Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy[J]. Semin Oncol, 2016, 43(6): 676-681. doi: 10.1053/j.seminoncol.2016.11.004
|
| [2] |
Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma[J]. Nat Rev Dis Primers, 2017, 3: 17046. doi: 10.1038/nrdp.2017.46
|
| [3] |
Bianchi G, Anderson KC. Understanding biology to tackle the disease: Multiple myeloma from bench to bedside, and back[J]. CA Cancer J Clin, 2014, 64(6): 422-444. doi: 10.3322/caac.21252
|
| [4] |
Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome[J]. N Engl J Med, 1996, 335(2): 91-97. doi: 10.1056/NEJM199607113350204
|
| [5] |
Mark T, Niesvizky R, Coleman M. Novel agents in myeloma: an exciting saga[J]. Cancer, 2009, 115(2): 236-242. doi: 10.1002/cncr.24040
|
| [6] |
Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma[J]. Blood, 2008, 111(5): 2521-2526. doi: 10.1182/blood-2007-08-104984
|
| [7] |
Kyle RA, Rajkumar SV. Multiple myeloma[J]. Blood, 2008, 111(6): 2962-2972. doi: 10.1182/blood-2007-10-078022
|
| [8] |
de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors[J]. J Immunol, 2011, 186(3): 1840-1848. doi: 10.4049/jimmunol.1003032
|
| [9] |
Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma[J]. N Engl J Med, 2015, 373(13): 1207-1219. doi: 10.1056/NEJMoa1506348
|
| [10] |
Sherbenou DW, Mark TM, Forsberg P. Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future[J]. Clin Lymphoma Myeloma Leuk, 2017, 17(9): 545-554. . doi: 10.1016/j.clml.2017.06.030
|
| [11] |
Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma[J]. N Engl J Med, 2016, 375(14): 1319-1331. doi: 10.1056/NEJMoa1607751
|
| [12] |
Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma[J]. N Engl J Med, 2019, 380(22): 2104-2115. doi: 10.1056/NEJMoa1817249
|
| [13] |
Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study[J]. Lancet, 2019, 394(10214): 2096-2107. doi: 10.1016/S0140-6736(19)32556-5
|
| [14] |
Martin TG, Corzo K, Chiron M, et al. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab[J]. Cells, 2019, 8(12): 1522. doi: 10.3390/cells8121522
|
| [15] |
Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma[J]. N Engl J Med, 2015, 373(7): 621-631. doi: 10.1056/NEJMoa1505654
|
| [16] |
Rosenblatt J, Avigan D. Targeting the PD-1/PD-L1 axis in multiple myeloma: a dream or a reality?[J]. Blood, 2017, 129(3): 275-279. doi: 10.1182/blood-2016-08-731885
|
| [17] |
Davis MP, Dickerson ED. Thalidomide: dual benefits in palliative medicine and oncology[J]. Am J Hosp Palliat Care, 2001, 18(5): 347-351. doi: 10.1177/104990910101800511
|
| [18] |
Badros A, Hyjek E, Ma N, et al. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma[J]. Blood, 2017, 130(10): 1189-1197. doi: 10.1182/blood-2017-03-775122
|
| [19] |
Mateos MV, Blacklock H, Schjesvold F, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial[J]. Lancet Haematol, 2019, 6(9): e459-e469. doi: 10.1016/S2352-3026(19)30110-3
|
| [20] |
Tai YT, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma[J]. Blood, 2014, 123(20): 3128-3138. doi: 10.1182/blood-2013-10-535088
|
| [21] |
Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial[J]. Lancet Oncol, 2018, 19(12): 1641-1653. doi: 10.1016/S1470-2045(18)30576-X
|
| [22] |
Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study[J]. Lancet Oncol, 2020, 21(2): 207-221. doi: 10.1016/S1470-2045(19)30788-0
|
| [23] |
Patel SV, Joshi N, Thareja T, et al. Corneal epithelial toxicity induced by belantamab mafodotin[J]. Clin Exp Ophthalmol, 2021, 49(9): 1113-1115. doi: 10.1111/ceo.13995
|
| [24] |
Teoh PJ, Chng WJ. CAR T-cell therapy in multiple myeloma: more room for improvement[J]. Blood Cancer J, 2021, 11(4): 84. doi: 10.1038/s41408-021-00469-5
|
| [25] |
Mikkilineni L, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for multiple myeloma[J]. Blood, 2017, 130(24): 2594-2602. doi: 10.1182/blood-2017-06-793869
|
| [26] |
Cho SF, Anderson KC, Tai YT. Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy[J]. Front Immunol, 2018, 9: 1821. doi: 10.3389/fimmu.2018.01821
|
| [27] |
Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma[J]. N Engl J Med, 2019, 380(18): 1726-1737. doi: 10.1056/NEJMoa1817226
|
| [28] |
Yan Z, Zhang H, Cao J, et al. Characteristics and Risk Factors of Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Treatment[J]. Front Immunol, 2021, 12: 611366. doi: 10.3389/fimmu.2021.611366
|
| [29] |
Berdeja JG, Madduri D, Usmani SZ, et al. 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[J]. Lancet, 2021, 398(10297): 314-324. doi: 10.1016/S0140-6736(21)00933-8
|
| [30] |
Lin Y, Martin T, Cohen AD, et al. Cytokine release syndrome in patients with relapsed/refractory multiple myeloma treated with ciltacabtagene autoleucel in the Phase 1b/2 CARTITUDE-1 Study[J]. Transplant Cell Ther, 2021, 27(3 Suppl): S43-S44.
|
| [31] |
Shah N, Alsina M, Siegel DS, et al. Initial results from a phase 1 clinical study of bb21217, a next-generation anti Bcma CAR T therapy[J]. Blood, 2018, 132(Suppl 1): 488.
|
| [32] |
Costello CL, Cohen AD, Patel KK, et al. 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[J]. Blood, 2020, 136(Suppl 1): 29-30.
|
| [33] |
Lancman G, Sastow DL, Cho HJ, et al. Bispecific Antibodies in Multiple Myeloma: Present and Future[J]. Blood Cancer Discov, 2021, 2(5): 423-433. doi: 10.1158/2643-3230.BCD-21-0028
|
| [34] |
Chari A, Berdeja JG, Oriol A, et al. A phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) x CD3 bispecific antibody, in patients with relapsed and/or refractory multiple myeloma (RRMM)[J]. Blood, 2020, 136(Suppl 1): 40-41.
|
| [35] |
Elkins K, Zheng B, Go M, et al. FcRL5 as a Target of Antibody-Drug Conjugates for the Treatment of Multiple Myeloma[J]. Mol Cancer Ther, 2012, 11(10): 2222-2232. doi: 10.1158/1535-7163.MCT-12-0087
|
| [36] |
Cohen AD, Harrison SJ, Krishnan A, et al. Initial Clinical Activity and Safety of BFCR4350A, a FcRH5/CD3 T-Cell-Engaging Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma[J]. Blood, 2020, 136(Suppl 1): 42-43.
|
| [37] |
Nishida H. Rapid Progress in Immunotherapies for Multiple Myeloma: An Updated Comprehensive Review[J]. Cancers (Basel), 2021, 13(11): 2712. doi: 10.3390/cancers13112712
|
| [38] |
Topp MS, Duell J, Zugmaier G, et al. Evaluation of AMG 420, an anti-BCMA bispecific T-cell engager (BiTE) immunotherapy, in R/R multiple myeloma (MM) patients: Updated results of a first-in-human (FIH) phaseⅠ dose escalation study[J]. J Clin Oncol, 2019, 37(15_suppl): 8007. doi: 10.1200/JCO.2019.37.15_suppl.8007
|
| [39] |
Topp MS, Duell J, Zugmaier G, et al. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma[J]. J Clin Oncol, 2020, 38(8): 775-783. doi: 10.1200/JCO.19.02657
|
| [40] |
Harrison SJ, Minnema MC, Lee HC, et al. A Phase 1 First in Human (FIH) Study of AMG 701, an Anti-B-Cell Maturation Antigen (BCMA) Half-Life Extended (HLE) BiTE® (bispecific T-cell engager) Molecule, in Relapsed/Refractory (RR) Multiple Myeloma (MM)[J]. Blood, 2020, 136(Suppl 1): 28-29.
|
| [41] |
Kumar SK, Harrison SJ, Cavo M, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial[J]. Lancet Oncol, 2020, 21(12): 1630-1642. doi: 10.1016/S1470-2045(20)30525-8
|
| [42] |
Kaufman JL, Gasparetto C, Schjesvold FH, et al. Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma[J]. Am J Hematol, 2021, 96(4): 418-427. doi: 10.1002/ajh.26083
|
| [43] |
Richter J, Madduri D, Richard S, et al. Selinexor in relapsed/refractory multiple myeloma[J]. Ther Adv Hematol, 2020, 11: 2040620720930629.
|
| [44] |
Vogl DT, Dingli D, Cornell RF, et al. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma[J]. J Clin Oncol, 2018, 36(9): 859-866. doi: 10.1200/JCO.2017.75.5207
|
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| [8] | Huo Hongxu, . Clinical study of monoclonal antibodies in bladder tumors[J]. Cancer Research on Prevention and Treatment, 1998, 25(2): 109-110. |
| [9] | Znang JiRon, . STUDY OF THE CORRESPONDING ANTIGEN OF A MONOCLONAL ANTIBODY (MGCI) AGAINST GASTRIC CANCER[J]. Cancer Research on Prevention and Treatment, 1991, 18(1): 1-2. |
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