627
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article

, &
Pages 33-57 | Received 15 Jun 2023, Accepted 07 Sep 2023, Published online: 15 Sep 2023

References

  • Kaseb H, Annamaraju P, Babiker HM. Monoclonal gammopathy of undetermined significance. In: StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC; 2022.
  • Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48. doi:10.1016/S1470-2045(14)70442-5
  • Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390. doi:10.1182/blood-2016-01-643569
  • Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom’s macroglobulinemia. J Clin Oncol. 2005;23(7):1564–1577. doi:10.1200/JCO.2005.03.144
  • ASCO. Cancer.net: ASCO; 2022.
  • Landgren O. Monoclonal gammopathy of undetermined significance and smoldering myeloma: new insights into pathophysiology and epidemiology. Hematology Am Soc Hematol Educ Program. 2010;2010:295–302. doi:10.1182/asheducation-2010.1.295
  • Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21–33. doi:10.4065/78.1.21
  • Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22):5418–5422. doi:10.1182/blood-2008-12-195008
  • Murray D, Kumar SK, Kyle RA, et al. Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement. Blood Cancer J. 2019;9(12):102. doi:10.1038/s41408-019-0263-z
  • Kyle RA, Larson DR, Therneau TM, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378(3):241–249. doi:10.1056/NEJMoa1709974
  • Thorsteinsdottir S, Kristinsson SY. The consultant’s guide to smoldering multiple myeloma. Hematology Am Soc Hematol Educ Program. 2022;2022(1):551–559. doi:10.1182/hematology.2022000355
  • Go RS, Rajkumar SV. How I manage monoclonal gammopathy of undetermined significance. Blood. 2018;131(2):163–173. doi:10.1182/blood-2017-09-807560
  • Waldenstrom J. Studies on conditions associated with disturbed gamma globulin formation (gammopathies). Harvey Lect. 1960;56:211–231.
  • Kyle RA. Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. Am J Med. 1978;64(5):814–826. doi:10.1016/0002-9343(78)90522-3
  • Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351(18):1860–1873. doi:10.1056/NEJMra041875
  • Pang L, Rajkumar SV, Kapoor P, et al. Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS). Blood Cancer J. 2021;11(2):26. doi:10.1038/s41408-021-00406-6
  • Therneau TM, Kyle RA, Melton LJ, et al. Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition. Mayo Clin Proc. 2012;87(11):1071–1079. doi:10.1016/j.mayocp.2012.06.014
  • van de Donk NW, Palumbo A, Johnsen HE, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica. 2014;99(6):984–996. doi:10.3324/haematol.2013.100552
  • Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106(3):812–817. doi:10.1182/blood-2005-03-1038
  • Kaseb H, Pavan A, Babiker HM. Monoclonal Gammopathy of Undetermined Significance. Treasure Island (FL): StatPearls; 2022.
  • Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356(25):2582–2590. doi:10.1056/NEJMoa070389
  • Akhlaghi T, Maclachlan K, Korde N, et al. P886: African American patients with smoldering multiple myeloma may have a lower risk of progression compared to white patients. HemaSphere. 2022;6:778–779. doi:10.1097/01.HS9.0000846420.96485.de
  • Ahn IE, Mailankody S, Korde N, Landgren O. Dilemmas in treating smoldering multiple myeloma. J Clin Oncol. 2015;33(1):115–123. doi:10.1200/JCO.2014.56.4351
  • Tessier C, Allard T, Boudreault J-S, et al. Testing Mayo clinic’s new 20/20/20 risk model in another cohort of smoldering Myeloma patients: a retrospective study. Curr Oncol. 2021;28(3):2029–2039. doi:10.3390/curroncol28030188
  • Mateos MV, Kumar S, Dimopoulos MA, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 2020;10(10):102. doi:10.1038/s41408-020-00366-3
  • Pérez-Persona E, Vidriales MB, Mateo G, et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood. 2007;110(7):2586–2592. doi:10.1182/blood-2007-05-088443
  • Vaxman I, Gertz MA. How I approach smoldering multiple myeloma. Blood. 2022;140(8):828–838. doi:10.1182/blood.2021011670
  • Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369(5):438–447. doi:10.1056/NEJMoa1300439
  • Lonial S, Jacobus S, Fonseca R, et al. Randomized trial of lenalidomide versus observation in smoldering multiple Myeloma. J Clin Oncol. 2020;38(11):1126–1137. doi:10.1200/JCO.19.01740
  • Mateos M-V, Martinez Lopez J, Rodríguez-Otero P, et al. Curative strategy (GEM-CESAR) for high-risk Smoldering Myeloma (SMM): carfilzomib, lenalidomide and dexamethasone (KRd) as induction followed by HDT-ASCT, consolidation with Krd and maintenance with Rd. Blood. 2021;138(Supplement 1):1829. doi:10.1182/blood-2021-148423
  • Kumar SK, Abdallah A-O, Badros AZ, et al. Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): a phase 2 trial of induction, consolidation and maintenance in subjects with high risk Smoldering Multiple Myeloma (SMM): initial analysis of safety Data. Blood. 2020;136(Supplement 1):35–36. doi:10.1182/blood-2020-142584
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA. 2020;70(1):7–30. doi:10.3322/caac.21590
  • Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple Myeloma: a review. JAMA. 2022;327(5):464–477. doi:10.1001/jama.2022.0003
  • Jurczyszyn A, Grzasko N, Gozzetti A, et al. Central nervous system involvement by multiple myeloma: a multi-institutional retrospective study of 172 patients in daily clinical practice. Am J Hematol. 2016;91(6):575–580. doi:10.1002/ajh.24351
  • Bahlis NJ, Lazarus HM. Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted? Bone Marrow Transplant. 2006;38(1):7–15. doi:10.1038/sj.bmt.1705395
  • Dupuis MM, Tuchman SA. Non-secretory multiple myeloma: from biology to clinical management. Onco Targets Ther. 2016;9:7583–7590. doi:10.2147/OTT.S122241
  • Ghobrial IM. Myeloma as a model for the process of metastasis: implications for therapy. Blood. 2012;120(1):20–30. doi:10.1182/blood-2012-01-379024
  • Gertz MA. Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management. Am J Hematol. 2021;96(2):258–269. doi:10.1002/ajh.26082
  • Fonseca R, Hayman S. Waldenström macroglobulinaemia. Br J Haematol. 2007;138(6):700–720. doi:10.1111/j.1365-2141.2007.06724.x
  • Groves FD, Travis LB, Devesa SS, Ries LA, Fraumeni JF. Waldenström’s macroglobulinemia: incidence patterns in the United States, 1988–1994. Cancer. 1998;82(6):1078–1081. doi:10.1002/(SICI)1097-0142(19980315)82:6<1078::AID-CNCR10>3.0.CO;2-3
  • Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter ZR, Treon SP. Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the surveillance, epidemiology and end results database. Br J Haematol. 2015;169(1):81–89. doi:10.1111/bjh.13264
  • Kyle RA, Larson DR, McPhail ED, et al. Fifty-year incidence of waldenström macroglobulinemia in Olmsted County, Minnesota, from 1961 through 2010: a population-based study with complete case capture and hematopathologic review. Mayo Clin Proc. 2018;93(6):739–746. doi:10.1016/j.mayocp.2018.02.011
  • Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenström’s macroglobulinemia: clinical features, complications, and management. J Clin Oncol. 2000;18(1):214–226. doi:10.1200/JCO.2000.18.1.214
  • García-Sanz R, Montoto S, Torrequebrada A, et al. Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol. 2001;115(3):575–582. doi:10.1046/j.1365-2141.2001.03144.x
  • Kyle RA, Ansell SM, Kapoor P. Prognostic factors and indications for treatment of Waldenström’s Macroglobulinemia. Best Pract Res Clin Haematol. 2016;29(2):179–186. doi:10.1016/j.beha.2016.08.014
  • Pavy MD, Murphy PL, Virella G. Paraprotein-induced hyperviscosity. A reversible cause of stroke. Postgrad Med. 1980;68(3):109–112. doi:10.1080/00325481.1980.11715533
  • Mueller J, Hotson JR, Langston JW. Hyperviscosity-induced dementia. Neurology. 1983;33(1):101–103. doi:10.1212/WNL.33.1.101
  • Bloch KJ, Maki DG. Hyperviscosity syndromes associated with immunoglobulin abnormalities. Semin Hematol. 1973;10(2):113–124.
  • Nobile-Orazio E, Marmiroli P, Baldini L, et al. Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M proteins. Neurology. 1987;37(9):1506–1514. doi:10.1212/WNL.37.9.1506
  • Chad DA, Harris NL. Case records of the Massachusetts general hospital. Weekly clinicopathological exercises. Case 16-1999. A 71-year-old man with progressive weakness and a gammopathy. N Engl J Med. 1999;340(21):1661–1669. doi:10.1056/NEJM199905273402108
  • Charakidis M, Russell DJ. Spontaneous splenic rupture in Waldenstrom’s macroglobulinemia: a case report. J Med Case Rep. 2010;4:300. doi:10.1186/1752-1947-4-300
  • Owen RG, Treon SP, Al-Katib A, et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the second international workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003;30(2):110–115. doi:10.1053/sonc.2003.50082
  • Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström’s macroglobulinemia. N Engl J Med. 2012;367(9):826–833. doi:10.1056/NEJMoa1200710
  • Zanwar S, Abeykoon JP. Treatment paradigm in Waldenström macroglobulinemia: frontline therapy and beyond. Ther Adv Hematol. 2022;13:20406207221093962. doi:10.1177/20406207221093962
  • Ihne S, Morbach C, Sommer C, Geier A, Knop S, Störk S. Amyloidosis-the diagnosis and treatment of an underdiagnosed disease. Dtsch Arztebl Int. 2020;117(10):159–166. doi:10.3238/arztebl.2020.0159
  • ASCO. Amyloidosis: statistics; 2022.
  • Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2(10):1046–1053. doi:10.1182/bloodadvances.2018016402
  • Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799–2806. doi:10.1093/eurheartj/ehx589
  • Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215–219. doi:10.1080/13506129.2018.1549825
  • Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis? Blood. 2016;128(2):159–168. doi:10.1182/blood-2016-01-629790
  • Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86(9):1036–1043. doi:10.1136/jnnp-2014-308724
  • Muchtar E, Dispenzieri A, Magen H, et al. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med. 2021;289(3):268–292. doi:10.1111/joim.13169
  • Ash S, Shorer E, Ramgobin D, et al. Cardiac amyloidosis-A review of current literature for the practicing physician. Clin Cardiol. 2021;44(3):322–331. doi:10.1002/clc.23572
  • Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med. 2012;79(6):733–748. doi:10.1002/msj.21352
  • Rowe K, Pankow J, Nehme F, Salyers W. Gastrointestinal Amyloidosis: review of the Literature. Cureus. 2017;9(5):e1228. doi:10.7759/cureus.1228
  • Pinto V, Bergantim R, Caires HR, Seca H, Guimarães JE, Vasconcelos MH. Multiple myeloma: available therapies and causes of drug resistance. Cancers. 2020;12(2):407. doi:10.3390/cancers12020407
  • Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple Myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228–1263. doi:10.1200/JCO.18.02096
  • Harousseau JL. How to select among available options for the treatment of multiple myeloma. Ann Oncol. 2012;23(Suppl 10):x334–8. doi:10.1093/annonc/mds311
  • Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma. Nat Rev Dis Primers. 2017;3:17046. doi:10.1038/nrdp.2017.46
  • Rajkumar SV. Multiple myeloma: 2018 update on diagnosis, risk‐stratification, and management. Am J Hematol. 2018;93(8):981–1114. doi:10.1002/ajh.25117
  • Kumar SK. Recycling therapies for myeloma: the need for prospective trials. Cancer. 2019;125(17):2920–2922. doi:10.1002/cncr.32177
  • Poczta A, Rogalska A, Marczak A. Treatment of multiple Myeloma and the role of melphalan in the era of modern therapies-current research and clinical approaches. J Clin Med. 2021;10(9):1841. doi:10.3390/jcm10091841
  • Dima D, Jiang D, Singh DJ, et al. Multiple Myeloma therapy: emerging trends and challenges. Cancers. 2022;14(17):4082. doi:10.3390/cancers14174082
  • Mateos MV, Bladé J, Bringhen S, et al. Melflufen: a peptide-drug conjugate for the treatment of multiple myeloma. J Clin Med. 2020;9(10):3120. doi:10.3390/jcm9103120
  • Ito S. Proteasome inhibitors for the treatment of multiple Myeloma. Cancers. 2020;12(2):265. doi:10.3390/cancers12020265
  • Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood. 2012;120(5):947–959. doi:10.1182/blood-2012-04-403733
  • Herndon TM, Deisseroth A, Kaminskas E, et al. U.S. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma. Clin Cancer Res. 2013;19(17):4559–4563. doi:10.1158/1078-0432.CCR-13-0755
  • Efentakis P, Kremastiotis G, Varela A, et al. Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin. Blood. 2019;133(7):710–723. doi:10.1182/blood-2018-06-858415
  • Tzogani K, Florez B, Markey G, et al. European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO Open. 2019;4(5):e000570. doi:10.1136/esmoopen-2019-000570
  • Sharma S, Lichtenstein A. Dexamethasone-induced apoptotic mechanisms in myeloma cells investigated by analysis of mutant glucocorticoid receptors. Blood. 2008;112(4):1338–1345. doi:10.1182/blood-2007-11-124156
  • Friedenberg WR, Kyle RA, Knospe WH, Bennett JM, Tsiatis AA, Oken MM. High-dose dexamethasone for refractory or relapsing multiple myeloma. Am J Hematol. 1991;36(3):171–175. doi:10.1002/ajh.2830360303
  • Kumar SK, Laubach JP, Giove TJ, et al. Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. Br J Haematol. 2017;178(5):756–763. doi:10.1111/bjh.14754
  • Devarakonda S, Efebera Y, Sharma N. Role of stem cell transplantation in multiple Myeloma. Cancers. 2021;13(4):863. doi:10.3390/cancers13040863
  • McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983;2(8354):822–824. doi:10.1016/S0140-6736(83)90739-0
  • Barlogie B, Alexanian R, Dicke KA, et al. High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood. 1987;70(3):869–872. doi:10.1182/blood.V70.3.869.869
  • Wildes TM, Finney JD, Fiala M, et al. High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma. Bone Marrow Transplant. 2015;50(8):1075–1082. doi:10.1038/bmt.2015.106
  • Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905. doi:10.1056/NEJMoa1402888
  • Cavo M, Gay F, Beksac M, et al. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020;7(6):e456–e68. doi:10.1016/S2352-3026(20)30099-5
  • Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311–1320. doi:10.1056/NEJMoa1611750
  • Gay F, Oliva S, Petrucci MT, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015;16(16):1617–1629. doi:10.1016/S1470-2045(15)00389-7
  • Kumar L, Hussain MM, Chethan R, et al. Multiple Myeloma: impact of time to transplant on the outcome. Clin Lymphoma Myeloma Leuk. 2022;22(9):e826–e35. doi:10.1016/j.clml.2022.04.020
  • Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): the phase 3 DETERMINATION trial. J Clin Oncol. 2022;40(17_suppl):LBA4–LBA. doi:10.1200/JCO.2022.40.17_suppl.LBA4
  • Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010;24(Suppl 1):S13–9. doi:10.1016/S0268-960X(10)70004-7
  • Sedlarikova L, Kubiczkova L, Sevcikova S, Hajek R. Mechanism of immunomodulatory drugs in multiple myeloma. Leuk Res. 2012;36(10):1218–1224. doi:10.1016/j.leukres.2012.05.010
  • Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357(21):2123–2132. doi:10.1056/NEJMoa070594
  • Rajkumar SV. Thalidomide: tragic past and promising future. Mayo Clin Proc. 2004;79(7):899–903. doi:10.4065/79.7.899
  • Cavo M, Pantani L, Petrucci MT, et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012;120(1):9–19. doi:10.1182/blood-2012-02-408898
  • Moreau P, Hulin C, Macro M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016;127(21):2569–2574. doi:10.1182/blood-2016-01-693580
  • Hipp S, Tai YT, Blanset D, et al. A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia. 2017;31(8):1743–1751. doi:10.1038/leu.2016.388
  • Rosiñol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019;134(16):1337–1345. doi:10.1182/blood.2019000241
  • Cho SF, Lin L, Xing L, et al. The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models. Blood Adv. 2020;4(17):4195–4207. doi:10.1182/bloodadvances.2020002524
  • Lonial S, Popat R, Hulin C, et al. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022;9(11):e822–e32. doi:10.1016/S2352-3026(22)00290-3
  • Richardson PG, Trudel S, Quach H, et al. Mezigdomide (CC-92480), a potent, novel Cereblon E3 Ligase Modulator (CELMoD), combined with Dexamethasone (DEX) in patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): preliminary results from the dose-expansion phase of the CC-92480-MM-001 trial. Blood. 2022;140(Supplement 1):1366–1368.
  • Lasica M, Anderson MA. Review of Venetoclax in CLL, AML and multiple Myeloma. J Pers Med. 2021;11(6):463. doi:10.3390/jpm11060463
  • Krejcik J, Casneuf T, Nijhof IS, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128(3):384–394. doi:10.1182/blood-2015-12-687749
  • Bobin A, Leleu X. Recent advances in the treatment of multiple myeloma: a brief review. Fac Rev. 2022;11:28. doi:10.12703/r/11-28
  • Ghobrial I, Cruz CH, Garfall A, et al. Immunotherapy in multiple Myeloma: accelerating on the path to the patient. Clin Lymphoma Myeloma Leuk. 2019;19(6):332–344. doi:10.1016/j.clml.2019.02.004
  • Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518–528. doi:10.1056/NEJMoa1714678
  • Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104–2115. doi:10.1056/NEJMoa1817249
  • Moreau P, Attal M, Hulin C, et al. 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. Lancet. 2019;394(10192):29–38. doi:10.1016/S0140-6736(19)31240-1
  • Collins SM, Bakan CE, Swartzel GD, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013;62(12):1841–1849. doi:10.1007/s00262-013-1493-8
  • Wudhikarn K, Wills B, Lesokhin AM. Monoclonal antibodies in multiple myeloma: current and emerging targets and mechanisms of action. Best Pract Res Clin Haematol. 2020;33(1):101143. doi:10.1016/j.beha.2020.101143
  • Seckinger A, Delgado JA, Moser S, et al. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017;31(3):396–410. doi:10.1016/j.ccell.2017.02.002
  • Tai YT, Acharya C, An G, et al. April and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127(25):3225–3236. doi:10.1182/blood-2016-01-691162
  • Ghermezi M, Li M, Vardanyan S, et al. Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients. Haematologica. 2017;102(4):785–795. doi:10.3324/haematol.2016.150896
  • Martin T, Usmani SZ, Berdeja JG, et al. 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. J Clin Oncol. 2023;41(6):1265–1274. doi:10.1200/JCO.22.00842
  • Smith EL, Harrington K, Staehr M, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med. 2019;11(485). doi:10.1126/scitranslmed.aau7746
  • Wong SW, Bar N, Paris L, et al. Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): results from a phase 1 first-in-human clinical study. Blood. 2022;140(Supplement 1):400–402. doi:10.1182/blood-2022-159009
  • Bumma N, Richter JR, Dhodapkar MV, et al. LINKER-MM1 study: linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41(16_suppl):8006. doi:10.1200/JCO.2023.41.16_suppl.8006
  • Topp MS, Duell J, Zugmaier G, et al. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. J Clin Oncol. 2020;38(8):775–783. doi:10.1200/JCO.19.02657
  • Cho SF, Yeh TJ, Anderson KC, Tai YT. Bispecific antibodies in multiple myeloma treatment: a journey in progress. Front Oncol. 2022;12:1032775. doi:10.3389/fonc.2022.1032775
  • Tan CR, Shah UA. Targeting BCMA in Multiple Myeloma. Curr Hematol Malig Rep. 2021;16(5):367–383. doi:10.1007/s11899-021-00639-z
  • Pillarisetti K, Powers G, Luistro L, et al. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020;4(18):4538–4549. doi:10.1182/bloodadvances.2020002393
  • Frerichs KA, Broekmans MEC, Marin Soto JA, et al. Preclinical activity of JNJ-7957, a novel BCMA×CD3 bispecific antibody for the treatment of multiple myeloma, is potentiated by daratumumab. Clin Cancer Res. 2020;26(9):2203–2215. doi:10.1158/1078-0432.CCR-19-2299
  • Janssen Research & Development, LLC. Janssen research & development; 2020.
  • Verkleij CPM, Broekmans MEC, van Duin M, et al. Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Adv. 2021;5(8):2196–2215. doi:10.1182/bloodadvances.2020003805
  • Pillarisetti K, Edavettal S, Mendonça M, et al. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020;135(15):1232–1243. doi:10.1182/blood.2019003342
  • Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232–2244. doi:10.1056/NEJMoa2204591
  • Lesokhin AM, Richter J, Trudel S, et al. Enduring responses after 1-year, fixed-duration cevostamab therapy in patients with relapsed/refractory multiple myeloma: early experience from a phase I study. Blood. 2022;140(Supplement 1):4415–4417. doi:10.1182/blood-2022-157547
  • Raje N, Bahlis NJ, Costello C, et al. Elranatamab, a BCMA targeted T-cell engaging bispecific antibody, induces durable clinical and molecular responses for patients with relapsed or refractory multiple myeloma. Blood. 2022;140(Supplement 1):388–390. doi:10.1182/blood-2022-166494
  • Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19(8):2048–2060. doi:10.1158/1078-0432.CCR-12-2422
  • Rendo MJ, Joseph JJ, Phan LM, DeStefano CB. CAR T-cell therapy for patients with multiple myeloma: current evidence and challenges. Blood Lymphat Cancer. 2022;12:119–136. doi:10.2147/BLCTT.S327016
  • Study of bb21217 in multiple myeloma; 2021.
  • bluebird bio. A Phase 1 Study of bb21217, an Anti-BCMA CAR T Cell Drug Product, in Relapsed and/or Refractory Multiple Myeloma [Internet]. clinicaltrials.gov; 2021 Mar [cited 2023 Sep 11]. Report No.: NCT03274219. Available from: https://clinicaltrials.gov/study/NCT03274219.
  • Juno Therapeutics, a Subsidiary of Celgene. A Phase I, Multi Center, Open Label Study of CC-98633, BCMA Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed and/or Refractory Multiple Myeloma [Internet]. clinicaltrials.gov; 2023 Feb [cited 2023 Sep 11]. Report No.: NCT04394650. Available from: https://clinicaltrials.gov/study/NCT04394650.
  • clinicaltrial.gov. BCMA Targeted CAR T Cells With or Without Lenalidomide for the Treatment of Multiple Myeloma. NCT03070327; Available from: https://classic.clinicaltrials.gov/ct2/show/NCT03070327.
  • Latorre SV. Pilot Study of the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-BCMA (TNFRSF17) Specificity Humanized Conjugated With the Co-stimulatory Region 4-1BB and Signal-transduction CD3z (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma With Previous Treatment With Proteasome Inhibitor, Immunomodulatory Drug and Anti-CD38 Monoclonal Antibody [Internet]. clinicaltrials.gov; 2023 Aug [cited 2023 Sep 11]. Report No.: NCT04309981. Available from: https://clinicaltrials.gov/study/NCT04309981.
  • clinicaltrial.gov. T cells expressing a novel fully-human anti-BCMA CAR for treating multiple myeloma. NCT03602612; 2023.
  • clinicaltrial.gov. BCMA-directed CAR-T cell therapy in adult patients with multiple myeloma. NCT04318327; 2023.
  • Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380(18):1726–1737. doi:10.1056/NEJMoa1817226
  • Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–716. doi:10.1056/NEJMoa2024850
  • Cohen AD, Mateos MV, Cohen YC, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023;141(3):219–230. doi:10.1182/blood.2022015526
  • Parikh RH, Lonial S. Chimeric antigen receptor T-cell therapy in multiple myeloma: a comprehensive review of current data and implications for clinical practice. CA. 2023;73(3):275–285. doi:10.3322/caac.21771
  • Castella M, Fernández de Larrea C, Martín-Antonio B. Immunotherapy: a novel era of promising treatments for multiple myeloma. Int J Mol Sci. 2018;19(11):3613. doi:10.3390/ijms19113613
  • Shimony S, Stone RM, Stahl M. Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. Curr Opin Hematol. 2022;29(2):63–73. doi:10.1097/MOH.0000000000000698
  • Slomp A, Moesbergen LM, Gong J-N, et al. Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting. Blood Adv. 2019;3(24):4202–4214. doi:10.1182/bloodadvances.2019000702
  • ClinicalTrials.gov. Novartis Pharmaceuticals. NCT04702425; 2023.
  • ClinicalTrials.gov. A study of PRT1419 in patients with relapsed/refractory hematologic malignancies. NCT04543305; 2023.
  • Caenepeel S, Brown SP, Belmontes B, et al. AMG 176, a selective MCL1 inhibitor, is effective in hematologic cancer models alone and in combination with established therapies. Cancer Discov. 2018;8(12):1582–1597. doi:10.1158/2159-8290.CD-18-0387
  • Chari A, Cornell RF, Gasparetto C, et al. Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma. Hematol Oncol. 2020;38(3):353–362. doi:10.1002/hon.2723
  • Von Suskil M, Sultana KN, Elbezanti WO, et al. Bruton’s tyrosine kinase targeting in multiple myeloma. Int J Mol Sci. 2021;22(11):5707. doi:10.3390/ijms22115707
  • ClinicalTrials.gov. Clinical research of adoptive BCMA CAR-NK cells on relapse/refractory MM. NCT03940833; 2023.
  • ClinicalTrials.gov. Anti-BCMA CAR-NK cell therapy for the relapsed or refractory multiple myeloma. NCT05008536; 2023.
  • Yang Y, Shi J, Gu Z, et al. Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer Res. 2015;75(3):594–604. doi:10.1158/0008-5472.CAN-14-2362
  • Elbezanti WO, Al-Odat OS, Chitren R, et al. Development of a novel Bruton’s tyrosine kinase inhibitor that exerts anti-cancer activities potentiates response of chemotherapeutic agents in multiple myeloma stem cell-like cells. Front Pharmacol. 2022;13:894535. doi:10.3389/fphar.2022.894535
  • Berdeja JG, Lin Y, Raje NS, et al. First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: updated results. J Clin Oncol. 2017;35(15_suppl):3010. doi:10.1200/JCO.2017.35.15_suppl.3010
  • Pittari G, Vago L, Festuccia M, et al. Restoring natural killer cell immunity against multiple myeloma in the era of new drugs. Front Immunol. 2017;8:1444. doi:10.3389/fimmu.2017.01444
  • Vogl DT, Kaufman JL, Holstein SA, et al. Modakafusp Alfa (TAK-573), an immunocytokine, shows clinical activity in patients with relapsed/refractory multiple myeloma; updated results from a first-in-human phase 1 study. Blood. 2021;138(Supplement 1):898. doi:10.1182/blood-2021-148463