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Abstract

Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted therapies (selinexor, venetoclax), chimeric antigen receptor T cells, T cell–engaging bispecific antibodies, and antibody–drug conjugates. For each modality, mechanism of action and clinical considerations are discussed. These therapies are combined and sequenced in modern treatment pathways, discussed at the conclusion of the article, which have led to substantial improvements in outcomes for multiple myeloma patients in recent years.

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2024-01-29
2024-06-16
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Literature Cited

  1. 1.
    SEER 2023. Cancer stat facts: myeloma National Cancer Institute Surveillance, Epidemiology, and End Results Program https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed Aug. 29, 2023
    [Google Scholar]
  2. 2.
    Kyle RA, Larson DR, Therneau TM et al. 2018. Long-term follow-up of monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 378:324149
    [Google Scholar]
  3. 3.
    Mateos M-V, Kumar S, Dimopoulos MA et al. 2020. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 10:10102
    [Google Scholar]
  4. 4.
    Landgren O, Weiss BM. 2009. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia 23:10169197
    [Google Scholar]
  5. 5.
    Siegel RL, Miller KD, Wagle NS et al. 2023. Cancer statistics, 2023. CA: Cancer J. Clinicians 73:11748
    [Google Scholar]
  6. 6.
    Joseph NS, Kaufman JL, Dhodapkar MV et al. 2020. Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J. Clin. Oncol. 38:17192837
    [Google Scholar]
  7. 7.
    González D, van der Burg M, García-Sanz R et al. 2007. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood 110:9311221
    [Google Scholar]
  8. 8.
    Barwick BG, Gupta VA, Vertino PM et al. 2019. Cell of origin and genetic alterations in the pathogenesis of multiple myeloma. Front. Immunol. 10:1121
    [Google Scholar]
  9. 9.
    Bustoros M, Sklavenitis-Pistofidis R, Park J et al. 2020. Genomic profiling of smoldering multiple myeloma identifies patients at a high risk of disease progression. J. Clin. Oncol. 38:21238089
    [Google Scholar]
  10. 10.
    Bailur JK, McCachren SS, Doxie DB et al. 2019. Early alterations in stem-like/marrow-resident T cells and innate and myeloid cells in preneoplastic gammopathy. JCI Insight 4:11e127807
    [Google Scholar]
  11. 11.
    Dhodapkar MV, Sexton R, Das R et al. 2015. Prospective analysis of antigen-specific immunity, stem-cell antigens, and immune checkpoints in monoclonal gammopathy. Blood 126:22247578
    [Google Scholar]
  12. 12.
    Boise LH, Kaufman JL, Bahlis NJ et al. 2014. The Tao of myeloma. Blood 124:12187379
    [Google Scholar]
  13. 13.
    Allman D. 2021. To build a plasma cell. Immunol. Rev. 303:157
    [Google Scholar]
  14. 14.
    Shaffer AL, Emre NCT, Lamy L et al. 2008. IRF4 addiction in multiple myeloma. Nature 454:720122631
    [Google Scholar]
  15. 15.
    Tai YT, Acharya C, An G et al. 2016. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood 127:25322536
    [Google Scholar]
  16. 16.
    Leone P, Solimando AG, Malerba E et al. 2020. Actors on the scene: immune cells in the myeloma niche. Front. Oncol. 10:599098
    [Google Scholar]
  17. 17.
    Burwick N, Sharma S. 2019. Glucocorticoids in multiple myeloma: past, present, and future. Ann. Hematol. 98:11928
    [Google Scholar]
  18. 18.
    Singhal S, Mehta J, Desikan R et al. 1999. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341:21156571
    [Google Scholar]
  19. 19.
    Ito T, Ando H, Suzuki T et al. 2010. Identification of a primary target of thalidomide teratogenicity. Science 327:5971134550
    [Google Scholar]
  20. 20.
    Krönke J, Udeshi ND, Narla A et al. 2014. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343:61683015
    [Google Scholar]
  21. 21.
    Lu G, Middleton RE, Sun H et al. 2014. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343:61683059
    [Google Scholar]
  22. 22.
    Hideshima T, Ogiya D, Liu J et al. 2021. Immunomodulatory drugs activate NK cells via both Zap-70 and cereblon-dependent pathways. Leukemia 35:117788
    [Google Scholar]
  23. 23.
    Davies FE, Raje N, Hideshima T et al. 2001. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 98:121016
    [Google Scholar]
  24. 24.
    Thakurta A, Pierceall WE, Amatangelo MD et al. 2021. Developing next generation immunomodulatory drugs and their combinations in multiple myeloma. Oncotarget 12:15155563
    [Google Scholar]
  25. 25.
    Bird SA, Pawlyn C. 2023. IMiD resistance in multiple myeloma: current understanding of the underpinning biology and clinical impact. Blood 142:213140
    [Google Scholar]
  26. 26.
    Lonial S, Popat R, Hulin C et al. 2022. 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. 9:11e82232
    [Google Scholar]
  27. 27.
    Richardson PG, Trudel S, Quach H et al. 2022. 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 140:Suppl. 1136668
    [Google Scholar]
  28. 28.
    Békés M, Langley DR, Crews CM. 2022. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug. Discov. 21:3181200
    [Google Scholar]
  29. 29.
    Obeng EA, Carlson LM, Gutman DM et al. 2006. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 107:12490716
    [Google Scholar]
  30. 30.
    Kisselev AF, Goldberg AL. 2001. Proteasome inhibitors: from research tools to drug candidates. Chem. Biol. 8:873958
    [Google Scholar]
  31. 31.
    Orlowski RZ, Kuhn DJ. 2008. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin. Cancer Res. 14:6164957
    [Google Scholar]
  32. 32.
    Arastu-Kapur S, Anderl JL, Kraus M et al. 2011. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin. Cancer Res. 17:9273443
    [Google Scholar]
  33. 33.
    Cornell RF, Ky B, Weiss BM et al. 2019. Prospective study of cardiac events during proteasome inhibitor therapy for relapsed multiple myeloma. J. Clin. Oncol. 37:22194655
    [Google Scholar]
  34. 34.
    Waxman AJ, Clasen S, Hwang WT et al. 2018. Carfilzomib-associated cardiovascular adverse events a systematic review and meta-analysis. JAMA Oncol. 4:3e174519
    [Google Scholar]
  35. 35.
    Moscvin M, Liacos CI, Chen T et al. 2023. Mutations in the alternative complement pathway in multiple myeloma patients with carfilzomib-induced thrombotic microangiopathy. Blood Cancer J. 13:131
    [Google Scholar]
  36. 36.
    Orlowski RZ, Stinchcombe TE, Mitchell BS et al. 2002. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J. Clin. Oncol. 20:22442027
    [Google Scholar]
  37. 37.
    Manasanch EE, Orlowski RZ. 2017. Proteasome inhibitors in cancer therapy. Nat. Rev. Clin. Oncol. 14:741733
    [Google Scholar]
  38. 38.
    Zhou X, Besse A, Peter J et al. 2020. High-dose carfilzomib achieves superior anti-tumor activity over low-dose and recaptures response in relapsed/refractory multiple myeloma resistant to low-dose carfilzomib by co-inhibiting the β2 and β1 subunits of the proteasome complex. Haematologica 108:6162839
    [Google Scholar]
  39. 39.
    Tai Y-T, Landesman Y, Acharya C et al. 2014. CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications. Leukemia 28:115565
    [Google Scholar]
  40. 40.
    Vogl DT, Dingli D, Cornell RF et al. 2018. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J. Clin. Oncol. 36:985966
    [Google Scholar]
  41. 41.
    Chari A, Vogl DT, Gavriatopoulou M et al. 2019. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N. Engl. J. Med. 381:872738
    [Google Scholar]
  42. 42.
    Grosicki S, Simonova M, Spicka I et al. 2020. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet 396:10262156373
    [Google Scholar]
  43. 43.
    Gupta VA, Barwick BG, Matulis SM et al. 2021. Venetoclax sensitivity in multiple myeloma is associated with B-cell gene expression. Blood 137:26360415
    [Google Scholar]
  44. 44.
    Kumar S, Kaufman JL, Gasparetto C et al. 2017. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood 130:2224019
    [Google Scholar]
  45. 45.
    Kumar SK, Harrison SJ, Cavo M et al. 2020. 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. Lancet Oncol. 21:12163042
    [Google Scholar]
  46. 46.
    van de Donk NWCJ, Usmani SZ. 2018. CD38 antibodies in multiple myeloma: mechanisms of action and modes of resistance. Front. Immunol. 9:2134
    [Google Scholar]
  47. 47.
    Lancman G, Arinsburg S, Jhang J et al. 2018. Blood transfusion management for patients treated with anti-CD38 monoclonal antibodies. Front. Immunol. 9:2616
    [Google Scholar]
  48. 48.
    Lokhorst HM, Plesner T, Laubach JP et al. 2015. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N. Engl. J. Med. 373:13120719
    [Google Scholar]
  49. 49.
    Deckert J, Wetzel M-C, Bartle LM et al. 2014. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin. Cancer Res. 20:17457483
    [Google Scholar]
  50. 50.
    Jiang H, Acharya C, An G et al. 2016. SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide. Leukemia 30:2399408
    [Google Scholar]
  51. 51.
    Mikhael J, Belhadj-Merzoug K, Hulin C et al. 2021. A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab. Blood Cancer J. 11:89
    [Google Scholar]
  52. 52.
    Hsi ED, Steinle R, Balasa B et al. 2008. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin. Cancer Res. 14:9277584
    [Google Scholar]
  53. 53.
    Tai Y-T, Dillon M, Song W et al. 2008. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood 112:4132937
    [Google Scholar]
  54. 54.
    Collins SM, Bakan CE, Swartzel GD et al. 2013. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol. Immunother. 62:12184149
    [Google Scholar]
  55. 55.
    Dimopoulos MA, Lonial S, White D et al. 2020. Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 10:991
    [Google Scholar]
  56. 56.
    Dimopoulos MA, Dytfeld D, Grosicki S et al. 2023. Elotuzumab plus pomalidomide and dexamethasone for relapsed/refractory multiple myeloma: final overall survival analysis from the randomized phase II ELOQUENT-3 trial. J. Clin. Oncol. 41:356878
    [Google Scholar]
  57. 57.
    Gill S, Brudno JN. 2021. CAR T-cell therapy in hematologic malignancies: clinical role, toxicity, and unanswered questions. Am. Soc. Clin. Oncol. Educ. Book 41:e24665
    [Google Scholar]
  58. 58.
    Lee DW, Santomasso BD, Locke FL et al. 2019. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol. Blood Marrow Transplant. 25:462538
    [Google Scholar]
  59. 59.
    Van Oekelen O, Aleman A, Upadhyaya B et al. 2021. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nat. Med. 27:122099103
    [Google Scholar]
  60. 60.
    Cohen AD, Parekh S, Santomasso BD et al. 2022. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 12:232
    [Google Scholar]
  61. 61.
    FDA 2021. ABECMA (idecabtagene vicleucel) Medication guide, US Food Drug Adm. Silver Spring, MD: https://www.fda.gov/media/147055/download
    [Google Scholar]
  62. 62.
    Munshi NC, Anderson LD, Shah N et al. 2021. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 384:870516
    [Google Scholar]
  63. 63.
    Berdeja JG, Madduri D, Usmani SZ et al. 2021. 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. Lancet 398:1029731424
    [Google Scholar]
  64. 64.
    Rodriguez-Otero P, Ailawadhi S, Arnulf B et al. 2023. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N. Engl. J. Med. 388:11100214
    [Google Scholar]
  65. 65.
    San-Miguel J, Dhakal B, Yong K et al. 2023. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N. Engl. J. Med. 389:433547
    [Google Scholar]
  66. 66.
    Garfall AL, Dancy EK, Cohen AD et al. 2019. T-cell phenotypes associated with effective CAR T-cell therapy in postinduction versus relapsed multiple myeloma. Blood Adv. 3:19281215
    [Google Scholar]
  67. 67.
    Garfall AL, Cohen AD, Susanibar-Adaniya SP et al. 2023. Anti-BCMA/CD19 CAR T cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line therapy. Blood Cancer Discov. 4:211833
    [Google Scholar]
  68. 68.
    Mailankody S, Matous JV, Chhabra S et al. 2023. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nat. Med. 29:242229
    [Google Scholar]
  69. 69.
    Ghassemi S, Nunez-Cruz S, O'Connor RS et al. 2018. Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (CAR) T cells. Cancer Immunol. Res. 6:911009
    [Google Scholar]
  70. 70.
    Costa LJ, Kumar SK, Atrash S et al. 2022. Results from the first phase 1 clinical study of the B-cell maturation antigen (BCMA) nex T chimeric antigen receptor (CAR) T cell therapy CC-98633/BMS-986354 in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Blood 140:Suppl. 1136062
    [Google Scholar]
  71. 71.
    Da Vià MC, Dietrich O, Truger M et al. 2021. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat. Med. 27:461619
    [Google Scholar]
  72. 72.
    Cohen AD, Garfall AL, Stadtmauer EA et al. 2019. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J. Clin. Investig. 129:6221021
    [Google Scholar]
  73. 73.
    Pont MJ, Hill T, Cole GO et al. 2019. γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood 134:19158597
    [Google Scholar]
  74. 74.
    Cowan AJ, Pont M, Sather BD et al. 2021. Safety and efficacy of fully human BCMA CAR T cells in combination with a gamma secretase inhibitor to increase BCMA surface expression in patients with relapsed or refractory multiple myeloma. Blood 138:551
    [Google Scholar]
  75. 75.
    Smith EL, Harrington K, Staehr M et al. 2019. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci. Transl. Med. 11:485eaau7746
    [Google Scholar]
  76. 76.
    Mailankody S, Devlin SM, Landa J et al. 2022. GPRC5D-targeted CAR T cells for myeloma. N. Engl. J. Med. 387:131196206
    [Google Scholar]
  77. 77.
    Lejeune M, Köse MC, Duray E et al. 2020. Bispecific, T-cell-recruiting antibodies in B-cell malignancies. Front. Immunol. 11:762
    [Google Scholar]
  78. 78.
    Topp MS, Duell J, Zugmaier G et al. 2020. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. JCO 38:877583
    [Google Scholar]
  79. 79.
    Moreau P, Garfall AL, van de Donk NWCJ et al. 2022. Teclistamab in relapsed or refractory multiple myeloma. N. Engl. J. Med. 387:6495505
    [Google Scholar]
  80. 80.
    Chari A, Minnema MC, Berdeja JG et al. 2022. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N. Engl. J. Med. 387:24223244
    [Google Scholar]
  81. 81.
    Li J, Stagg NJ, Johnston J et al. 2017. Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing. Cancer Cell 31:338395
    [Google Scholar]
  82. 82.
    Trudel S, Cohen AD, Krishnan AY et al. 2021. 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. Blood 138:Suppl. 1157
    [Google Scholar]
  83. 83.
    Mazahreh F, Mazahreh L, Schinke C et al. 2023. Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis. Blood Adv. 7:13306974
    [Google Scholar]
  84. 84.
    Lesokhin AM, Richter J, Trudel S et al. 2022. Enduring responses after 1-year, fixed-duration cevostamab therapy in patients with relapsed/refractory multiple myeloma: early experience from a phase I study. Blood 140:Suppl. 1441517
    [Google Scholar]
  85. 85.
    Friedrich MJ, Neri P, Kehl N et al. 2023. The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients. Cancer Cell 41:471125.e6
    [Google Scholar]
  86. 86.
    Drago JZ, Modi S, Chandarlapaty S. 2021. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat. Rev. Clin. Oncol. 18:632744
    [Google Scholar]
  87. 87.
    Lonial S, Lee HC, Badros A et al. 2020. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 21:220721
    [Google Scholar]
  88. 88.
    Rajkumar SV. 2022. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am. J. Hematol. 97:81086107
    [Google Scholar]
  89. 89.
    Durie BGM, Hoering A, Abidi MH et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 389:1006851927
    [Google Scholar]
  90. 90.
    Facon T, Kumar SK, Plesner T et al. 2021. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 22:11158296
    [Google Scholar]
  91. 91.
    Kumar SK, Jacobus SJ, Cohen AD et al. 2020. Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 21:10131730
    [Google Scholar]
  92. 92.
    Voorhees PM, Kaufman JL, Laubach J et al. 2020. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood 136:893645
    [Google Scholar]
  93. 93.
    Moreau P, Hulin C, Perrot A et al. 2021. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 22:10137890
    [Google Scholar]
  94. 94.
    Attal M, Lauwers-Cances V, Hulin C et al. 2017. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N. Engl. J. Med. 376:14131120
    [Google Scholar]
  95. 95.
    Cavo M, Gay F, Beksac M et al. 2020. Upfront autologous hematopoietic stem-cell transplantation improves overall survival in comparison with bortezomib-based intensification therapy in newly diagnosed multiple myeloma: long-term follow-up analysis of the randomized phase 3 EMN02/HO95 study. Blood 136:Suppl. 13738
    [Google Scholar]
  96. 96.
    Richardson PG, Jacobus SJ, Weller EA et al. 2022. Triplet therapy, transplantation, and maintenance until progression in myeloma. N. Engl. J. Med. 387:213247
    [Google Scholar]
  97. 97.
    McCarthy PL, Holstein SA, Petrucci MT et al. 2017. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J. Clin. Oncol. 35:29327989
    [Google Scholar]
  98. 98.
    Jackson GH, Davies FE, Pawlyn C et al. 2019. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 20:15773
    [Google Scholar]
  99. 99.
    Paiva B, San-Miguel J, Avet-Loiseau H. 2022. MRD in multiple myeloma: Does CR really matter?. Blood 140:23242328
    [Google Scholar]
  100. 100.
    Raje N, Yee AJ. 2020. How we approach smoldering multiple myeloma. J. Clin. Oncol. 38:11111925
    [Google Scholar]
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