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Diagnosis and Management of Multiple MyelomaA Review

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To identify the key insights or developments described in this article
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Abstract

Importance  Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year.

Observations  Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization—t(4;14), del(17p), and t(14;16)—to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients.

Conclusions and Relevance  Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

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Article Information

Corresponding Author: Edward N. Libby, MD, University of Washington, Department of Internal Medicine, Division of Medical Oncology, 1144 Eastlake Ave E, LG-650, Seattle, Washington 98109 (elibby@seattlecca.org).

Accepted for Publication: January 4, 2022.

Author Contributions: Drs Cowan and Libby had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Cowan, Gopal, Libby.

Acquisition, analysis, or interpretation of data: Cowan, Green, Kwok, Lee, Coffey, Holmberg, Tuazon, Libby.

Drafting of the manuscript: Cowan, Tuazon, Libby.

Critical revision of the manuscript for important intellectual content: All authors.

Supervision: Cowan, Kwok, Gopal, Libby.

Conflict of Interest Disclosures: Dr Cowan reported receiving grants from Janssen, Abbvie, Bristol Myers Squibb, Nektar, Harpoon, and Sanofi and receiving personal fees from Cellectar, Janssen, Abbvie, GlaxoSmithKline, and Secura Bio. Dr Green reported receiving personal fees from Janssen Biotech, Juno Therapeutics, GlaxoSmithKline, Neuleukin Therapeutics, Seattle Genomics, Legend Biotech, Celgene, and Bristol Myers Squibb; receiving clinical trial support from Janssen Biotech, Seattle Genetics, Bristol Myers Squibb, Cellectar Biosciences, and Sanofi-Aventis; receiving grants from Juno Therapeutics and Spring Works Therapeutics; and having a patent 20210171651 pending and holding patent 20200289565, with royalties paid from Juno Therapeutics, a Bristol Myers Squibb Company. Dr Holmberg reported receiving study funding from Seattle Genetics, Sanofi, Millennium-Takada, Bristol Myers Squibb, Merck, and Janssen and holding a patent for Up-To-Date, with royalties paid. Dr Tuazon reported receiving grants from the Conquer Cancer Foundation and National Institutes of Health/National Cancer Institute (P30 CA015704). Dr Gopal reported receiving research funding and study drug from IgM, Agios, Bristol Myers Squibb, and Teva; receiving personal fees from Epizyme, Incyte, Kite, ADC, Karopharm, Nurix, and Cellectar; and receiving consulting fees, research funding, study materials, and/or other personal fees from Merck, Takeda, Gilead, A-Z, Janssen, SeaGen, and Pfizer. Dr Libby reported receiving research funding and study drug from Celgene, Janssen, GlaxoSmithKline, Genentech, BeiGene, and Millenium and receiving consulting fees from Alnylam, Abbvie, Pharmacyclics, Adaptive Biotechnologies, and Akcea. No other disclosures were reported.

Additional Information: Dr Tuazon was employed at the Fred Hutchinson Cancer Research Center for most of the time the manuscript was being developed.

References
1.
Siegel  RL , Miller  KD , Jemal  A .  Cancer statistics, 2020.   CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590PubMedGoogle ScholarCrossref
2.
Zhou  L , Yu  Q , Wei  G ,  et al.  Measuring the global, regional, and national burden of multiple myeloma from 1990 to 2019.   BMC Cancer. 2021;21(1):606. doi:10.1186/s12885-021-08280-yPubMedGoogle ScholarCrossref
3.
Surveillance, Epidemiology, and End Results (SEER) program populations (1969-2019). National Cancer Institute. Released February 2021. Accessed March 26, 2021. https://www.seer.cancer.gov/popdata
4.
LeMasters  GK , Genaidy  AM , Succop  P ,  et al.  Cancer risk among firefighters: a review and meta-analysis of 32 studies.   J Occup Environ Med. 2006;48(11):1189-1202. doi:10.1097/01.jom.0000246229.68697.90PubMedGoogle ScholarCrossref
5.
Birmann  BM , Andreotti  G , De Roos  AJ ,  et al.  Young adult and usual adult body mass index and multiple myeloma risk: a pooled analysis in the International Multiple Myeloma Consortium (IMMC).   Cancer Epidemiol Biomarkers Prev. 2017;26(6):876-885. doi:10.1158/1055-9965.EPI-16-0762-TPubMedGoogle ScholarCrossref
6.
Bertazzi  PA , Zocchetti  C , Guercilena  S ,  et al.  Dioxin exposure and cancer risk: a 15-year mortality study after the “Seveso accident”.   Epidemiology. 1997;8(6):646-652. doi:10.1097/00001648-199710000-00006PubMedGoogle Scholar
7.
Landgren  O , Zeig-Owens  R , Giricz  O ,  et al.  Multiple myeloma and its precursor disease among firefighters exposed to the World Trade Center disaster.   JAMA Oncol. 2018;4(6):821-827. doi:10.1001/jamaoncol.2018.0509PubMedGoogle ScholarCrossref
8.
Anderson  KC , Carrasco  RD .  Pathogenesis of myeloma.   Annu Rev Pathol. 2011;6:249-274. doi:10.1146/annurev-pathol-011110-130249PubMedGoogle ScholarCrossref
9.
Lightman  SM , Utley  A , Lee  KP .  Survival of long-lived plasma cells (LLPC): piecing together the puzzle.   Front Immunol. 2019;10(965):965. doi:10.3389/fimmu.2019.00965PubMedGoogle Scholar
10.
Ghobrial  IM .  Myeloma as a model for the process of metastasis: implications for therapy.   Blood. 2012;120(1):20-30. doi:10.1182/blood-2012-01-379024PubMedGoogle ScholarCrossref
11.
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-e548. doi:10.1016/S1470-2045(14)70442-5PubMedGoogle ScholarCrossref
12.
Multiple Myeloma (Version 7.2021). National Comprehensive Cancer Network. Accessed June 13, 2021. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf
13.
Crawford  J , Eye  MK , Cohen  HJ .  Evaluation of monoclonal gammopathies in the “well” elderly.   Am J Med. 1987;82(1):39-45. doi:10.1016/0002-9343(87)90375-5PubMedGoogle ScholarCrossref
14.
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/NEJMoa1709974PubMedGoogle ScholarCrossref
15.
Ravindran  A , Bartley  AC , Holton  SJ ,  et al.  Prevalence, incidence and survival of smoldering multiple myeloma in the United States.   Blood Cancer J. 2016;6(10):e486. doi:10.1038/bcj.2016.100PubMedGoogle Scholar
16.
Mateos  M-V , Hernández  M-T , 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/NEJMoa1300439PubMedGoogle ScholarCrossref
17.
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.19.01740PubMedGoogle ScholarCrossref
18.
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:10.4065/78.1.21PubMedGoogle ScholarCrossref
19.
Usmani  SZ , Heuck  C , Mitchell  A ,  et al.  Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents.   Haematologica. 2012;97(11):1761-1767. doi:10.3324/haematol.2012.065698PubMedGoogle ScholarCrossref
20.
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.24351PubMedGoogle ScholarCrossref
21.
Fernández de Larrea  C , Kyle  RA , Durie  BG ,  et al; International Myeloma Working Group.  Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group.   Leukemia. 2013;27(4):780-791. doi:10.1038/leu.2012.336PubMedGoogle ScholarCrossref
22.
Dhakal  B , Patel  S , Girnius  S ,  et al.  Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era.   Leukemia. 2020;34(12):3338-3347. doi:10.1038/s41375-020-0830-0PubMedGoogle ScholarCrossref
23.
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.1705395PubMedGoogle ScholarCrossref
24.
Dupuis  MM , Tuchman  SA .  Non-secretory multiple myeloma: from biology to clinical management.   Onco Targets Ther. 2016;9:7583-7590. doi:10.2147/OTT.S122241PubMedGoogle ScholarCrossref
25.
Baffour  FI , Glazebrook  KN , Kumar  SK , Broski  SM .  Role of imaging in multiple myeloma.   Am J Hematol. 2020;95(8):966-977. doi:10.1002/ajh.25846PubMedGoogle ScholarCrossref
26.
Hillengass  J , Moulopoulos  LA , Delorme  S ,  et al.  Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group.   Blood Cancer J. 2017;7(8):e599. doi:10.1038/bcj.2017.78PubMedGoogle Scholar
27.
Zamagni  E , Nanni  C , Patriarca  F ,  et al.  A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma.   Haematologica. 2007;92(1):50-55. doi:10.3324/haematol.10554PubMedGoogle ScholarCrossref
28.
Hillengass  J , Usmani  S , Rajkumar  SV ,  et al.  International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders.   Lancet Oncol. 2019;20(6):e302-e312. doi:10.1016/S1470-2045(19)30309-2PubMedGoogle ScholarCrossref
29.
Hillengass  J , Fechtner  K , Weber  MA ,  et al.  Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma.   J Clin Oncol. 2010;28(9):1606-1610. doi:10.1200/JCO.2009.25.5356PubMedGoogle ScholarCrossref
30.
Fonseca  R , Abouzaid  S , Bonafede  M ,  et al.  Trends in overall survival and costs of multiple myeloma, 2000-2014.   Leukemia. 2017;31(9):1915-1921. doi:10.1038/leu.2016.380PubMedGoogle ScholarCrossref
31.
Joseph  NS , Kaufman  JL , Dhodapkar  MV ,  et al.  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. 2020;38(17):1928-1937. doi:10.1200/JCO.19.02515PubMedGoogle ScholarCrossref
32.
Bergsagel  DE .  Is aggressive chemotherapy more effective in the treatment of plasma cell myeloma?   Eur J Cancer Clin Oncol. 1989;25(2):159-161. doi:10.1016/0277-5379(89)90001-1PubMedGoogle ScholarCrossref
33.
Palumbo  A , Avet-Loiseau  H , Oliva  S ,  et al.  Revised international staging system for multiple myeloma: a report from International Myeloma Working Group.   J Clin Oncol. 2015;33(26):2863-2869. doi:10.1200/JCO.2015.61.2267PubMedGoogle ScholarCrossref
34.
Saxe  D , Seo  E-J , Bergeron  MB , Han  J-Y .  Recent advances in cytogenetic characterization of multiple myeloma.   Int J Lab Hematol. 2019;41(1):5-14. doi:10.1111/ijlh.12882PubMedGoogle ScholarCrossref
35.
Mellors  PW , Binder  M , Ketterling  RP ,  et al.  Metaphase cytogenetics and plasma cell proliferation index for risk stratification in newly diagnosed multiple myeloma.   Blood Adv. 2020;4(10):2236-2244. doi:10.1182/bloodadvances.2019001275PubMedGoogle ScholarCrossref
36.
Chan  H , Phillips  M , Maganti  M ,  et al.  Single-center experience in treating patients with t(4;14) multiple myeloma with and without planned frontline autologous stem cell transplantation.   Clin Lymphoma Myeloma Leuk. 2018;18(3):225-234. doi:10.1016/j.clml.2017.12.009PubMedGoogle ScholarCrossref
37.
Lakshman  A , Painuly  U , Rajkumar  SV ,  et al.  Natural history of multiple myeloma with de novo del(17p).   Blood Cancer J. 2019;9(3):32. doi:10.1038/s41408-019-0191-yPubMedGoogle ScholarCrossref
38.
Ross  FM , Chiecchio  L , Dagrada  G ,  et al; UK Myeloma Forum.  The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significance.   Haematologica. 2010;95(7):1221-1225. doi:10.3324/haematol.2009.016329PubMedGoogle ScholarCrossref
39.
Schmidt  TM , Barwick  BG , Joseph  N ,  et al.  Gain of chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone.   Blood Cancer J. 2019;9(12):94. doi:10.1038/s41408-019-0254-0PubMedGoogle ScholarCrossref
40.
Walker  BA , Mavrommatis  K , Wardell  CP ,  et al.  A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis.   Leukemia. 2019;33(1):159-170. doi:10.1038/s41375-018-0196-8PubMedGoogle ScholarCrossref
41.
Avet-Loiseau  H , Attal  M , Moreau  P ,  et al.  Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.   Blood. 2007;109(8):3489-3495. doi:10.1182/blood-2006-08-040410PubMedGoogle ScholarCrossref
42.
Chang  H , Qi  C , Yi  QL , Reece  D , Stewart  AK .  p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation.   Blood. 2005;105(1):358-360. doi:10.1182/blood-2004-04-1363PubMedGoogle ScholarCrossref
43.
Fonseca  R , Blood  E , Rue  M ,  et al.  Clinical and biologic implications of recurrent genomic aberrations in myeloma.   Blood. 2003;101(11):4569-4575. doi:10.1182/blood-2002-10-3017PubMedGoogle ScholarCrossref
44.
Goldman-Mazur  S , Jurczyszyn  A , Castillo  JJ ,  et al.  A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma.   Am J Hematol. 2020;95(5):503-509. doi:10.1002/ajh.25758PubMedGoogle ScholarCrossref
45.
Weinhold  N , Ashby  C , Rasche  L ,  et al.  Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma.   Blood. 2016;128(13):1735-1744. doi:10.1182/blood-2016-06-723007PubMedGoogle ScholarCrossref
46.
Fonseca  R , Blood  EA , Oken  MM ,  et al.  Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients.   Blood. 2002;99(10):3735-3741. doi:10.1182/blood.V99.10.3735PubMedGoogle ScholarCrossref
47.
Lonial  S , Anderson  KC .  Association of response endpoints with survival outcomes in multiple myeloma.   Leukemia. 2014;28(2):258-268. doi:10.1038/leu.2013.220PubMedGoogle ScholarCrossref
48.
Dimopoulos  MA , Chen  C , Spencer  A ,  et al.  Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.   Leukemia. 2009;23(11):2147-2152. doi:10.1038/leu.2009.147PubMedGoogle ScholarCrossref
49.
Leleu  X , Attal  M , Arnulf  B ,  et al; Intergroupe Francophone du Myélome.  Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02.   Blood. 2013;121(11):1968-1975. doi:10.1182/blood-2012-09-452375PubMedGoogle ScholarCrossref
50.
Miguel  JS , Weisel  K , Moreau  P ,  et al.  Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial.   Lancet Oncol. 2013;14(11):1055-1066. doi:10.1016/S1470-2045(13)70380-2PubMedGoogle ScholarCrossref
51.
Rajkumar  SV , Jacobus  S , Callander  NS ,  et al; Eastern Cooperative Oncology Group.  Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial.   Lancet Oncol. 2010;11(1):29-37. doi:10.1016/S1470-2045(09)70284-0PubMedGoogle ScholarCrossref
52.
Rajkumar  SV , Rosiñol  L , Hussein  M ,  et al.  Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma.   J Clin Oncol. 2008;26(13):2171-2177. doi:10.1200/JCO.2007.14.1853PubMedGoogle ScholarCrossref
53.
Richardson  PG , Siegel  DS , Vij  R ,  et al.  Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.   Blood. 2014;123(12):1826-1832. doi:10.1182/blood-2013-11-538835PubMedGoogle ScholarCrossref
54.
Lu  G , Middleton  RE , Sun  H ,  et al.  The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins.   Science. 2014;343(6168):305-309. doi:10.1126/science.1244917PubMedGoogle ScholarCrossref
55.
Krönke  J , Fink  EC , Hollenbach  PW ,  et al.  Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.   Nature. 2015;523(7559):183-188. doi:10.1038/nature14610PubMedGoogle ScholarCrossref
56.
Ito  T , Ando  H , Suzuki  T ,  et al.  Identification of a primary target of thalidomide teratogenicity.   Science. 2010;327(5971):1345-1350. doi:10.1126/science.1177319PubMedGoogle ScholarCrossref
57.
Durie  BGM , Hoering  A , Sexton  R ,  et al.  Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT).   Blood Cancer J. 2020;10(5):53. doi:10.1038/s41408-020-0311-8PubMedGoogle ScholarCrossref
58.
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)31240-1PubMedGoogle ScholarCrossref
59.
Dimopoulos  MA , Moreau  P , Palumbo  A ,  et al; ENDEAVOR Investigators.  Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study.   Lancet Oncol. 2016;17(1):27-38. doi:10.1016/S1470-2045(15)00464-7PubMedGoogle ScholarCrossref
60.
Dimopoulos  MA , Goldschmidt  H , Niesvizky  R ,  et al.  Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.   Lancet Oncol. 2017;18(10):1327-1337. doi:10.1016/S1470-2045(17)30578-8PubMedGoogle ScholarCrossref
61.
Dimopoulos  M , Quach  H , Mateos  MV ,  et al.  Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.   Lancet. 2020;396(10245):186-197. doi:10.1016/S0140-6736(20)30734-0PubMedGoogle ScholarCrossref
62.
Stewart  AK , Rajkumar  SV , Dimopoulos  MA ,  et al; ASPIRE Investigators.  Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.   N Engl J Med. 2015;372(2):142-152. doi:10.1056/NEJMoa1411321PubMedGoogle ScholarCrossref
63.
Dimopoulos  MA , Špička  I , Quach  H ,  et al; TOURMALINE-MM4 Study Group.  Ixazomib as postinduction maintenance for patients with newly diagnosed multiple myeloma not undergoing autologous stem cell transplantation: the phase III TOURMALINE-MM4 trial.   J Clin Oncol. 2020;38(34):4030-4041. doi:10.1200/JCO.20.02060PubMedGoogle ScholarCrossref
64.
Moreau  P , Masszi  T , Grzasko  N ,  et al; TOURMALINE-MM1 Study Group.  Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma.   N Engl J Med. 2016;374(17):1621-1634. doi:10.1056/NEJMoa1516282PubMedGoogle ScholarCrossref
65.
Moreau  P , Mateos  MV , Berenson  JR ,  et al.  Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.   Lancet Oncol. 2018;19(7):953-964. doi:10.1016/S1470-2045(18)30354-1PubMedGoogle ScholarCrossref
66.
Voorhees  PM , Kaufman  JL , Laubach  J ,  et al.  Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial.   Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288PubMedGoogle ScholarCrossref
67.
Dimopoulos  MA , San-Miguel  J , Belch  A ,  et al.  Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX.   Haematologica. 2018;103(12):2088-2096. doi:10.3324/haematol.2018.194282PubMedGoogle ScholarCrossref
68.
Mateos  MV , Sonneveld  P , Hungria  V ,  et al.  Daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with previously treated multiple myeloma: three-year follow-up of CASTOR.   Clin Lymphoma Myeloma Leuk. 2020;20(8):509-518. doi:10.1016/j.clml.2019.09.623PubMedGoogle ScholarCrossref
69.
Dimopoulos  MA , Oriol  A , Nahi  H ,  et al; POLLUX Investigators.  Daratumumab, lenalidomide, and dexamethasone for multiple myeloma.   N Engl J Med. 2016;375(14):1319-1331. doi:10.1056/NEJMoa1607751PubMedGoogle ScholarCrossref
70.
Attal  M , Richardson  PG , Rajkumar  SV ,  et al; ICARIA-MM Study Group.  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.   Lancet. 2019;394(10214):2096-2107. doi:10.1016/S0140-6736(19)32556-5PubMedGoogle ScholarCrossref
71.
Dimopoulos  MA , Dytfeld  D , Grosicki  S ,  et al.  Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma.   N Engl J Med. 2018;379(19):1811-1822. doi:10.1056/NEJMoa1805762PubMedGoogle ScholarCrossref
72.
Facon  T , Kumar  S , Plesner  T ,  et al; MAIA Trial Investigators.  Daratumumab plus lenalidomide and dexamethasone for untreated myeloma.   N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249PubMedGoogle ScholarCrossref
73.
Lonial  S , Dimopoulos  M , Palumbo  A ,  et al; ELOQUENT-2 Investigators.  Elotuzumab therapy for relapsed or refractory multiple myeloma.   N Engl J Med. 2015;373(7):621-631. doi:10.1056/NEJMoa1505654PubMedGoogle ScholarCrossref
74.
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.   Lancet Oncol. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0PubMedGoogle ScholarCrossref
75.
Trudel  S , Lendvai  N , Popat  R ,  et al.  Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study.   Blood Cancer J. 2019;9(4):37. doi:10.1038/s41408-019-0196-6PubMedGoogle ScholarCrossref
76.
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.   Lancet Oncol. 2018;19(12):1641-1653. doi:10.1016/S1470-2045(18)30576-XPubMedGoogle ScholarCrossref
77.
Chari  A , Vogl  DT , Gavriatopoulou  M ,  et al.  Oral selinexor-dexamethasone for triple-class refractory multiple myeloma.   N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455PubMedGoogle ScholarCrossref
78.
Grosicki  S , Simonova  M , Spicka  I ,  et al.  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. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3PubMedGoogle ScholarCrossref
79.
Munshi  NC , Anderson  LD  Jr , Shah  N ,  et al.  Idecabtagene vicleucel in relapsed and refractory multiple myeloma.   N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850PubMedGoogle ScholarCrossref
80.
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/NEJMoa1817226PubMedGoogle ScholarCrossref
81.
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-e468. doi:10.1016/S2352-3026(20)30099-5PubMedGoogle ScholarCrossref
82.
Burwick  N , Sharma  S .  Glucocorticoids in multiple myeloma: past, present, and future.   Ann Hematol. 2019;98(1):19-28. doi:10.1007/s00277-018-3465-8PubMedGoogle ScholarCrossref
83.
San-Miguel  JF , Hungria  VTM , Yoon  S-S ,  et al.  Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial.   Lancet Oncol. 2014;15(11):1195-1206. doi:10.1016/S1470-2045(14)70440-1PubMedGoogle ScholarCrossref
84.
Kumar  SK , Jacobus  SJ , Cohen  AD ,  et al.  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. 2020;21(10):1317-1330. doi:10.1016/S1470-2045(20)30452-6PubMedGoogle ScholarCrossref
85.
Attal  M , Lauwers-Cances  V , Hulin  C ,  et al; IFM 2009 Study.  Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma.   N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/NEJMoa1611750PubMedGoogle ScholarCrossref
86.
Holstein  SA , Jung  SH , Richardson  PG ,  et al.  Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial.   Lancet Haematol. 2017;4(9):e431-e442. doi:10.1016/S2352-3026(17)30140-0PubMedGoogle ScholarCrossref
87.
Goldschmidt  H , Lokhorst  HM , Mai  EK ,  et al.  Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial.   Leukemia. 2018;32(2):383-390. doi:10.1038/leu.2017.211PubMedGoogle ScholarCrossref
88.
Stadtmauer  EA , Pasquini  MC , Blackwell  B ,  et al.  Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial.   J Clin Oncol. 2019;37(7):589-597. doi:10.1200/JCO.18.00685PubMedGoogle ScholarCrossref
89.
Cowan  AJ , Baldomero  H , Atsuta  Y ,  et al.  the global state of hematopoietic cell transplantation for multiple myeloma: an analysis of the Worldwide Network of Blood and Marrow Transplantation Database and the Global Burden of Disease Study.   Biol Blood Marrow Transplant. 2020;26(12):2372-2377. doi:10.1016/j.bbmt.2020.08.018PubMedGoogle ScholarCrossref
90.
Munshi  PN , Vesole  D , Jurczyszyn  A ,  et al.  Age no bar: a CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma.   Cancer. 2020;126(23):5077-5087. doi:10.1002/cncr.33171PubMedGoogle ScholarCrossref
91.
Delforge  M , Ludwig  H .  How I manage the toxicities of myeloma drugs.   Blood. 2017;129(17):2359-2367. doi:10.1182/blood-2017-01-725705PubMedGoogle ScholarCrossref
92.
Gagelman  N , Eikema  D-J , Koster  L ,  et al.  Tandem autologous stem cell transplantation improves outcomes in newly diagnosed multiple myeloma with extramedullary disease and high-risk cytogenetics: a study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.   Biol Blood Marrow Transplant. 2019;25(11):2134-2142. doi:10.1016/j.bbmt.2019.07.004PubMedGoogle ScholarCrossref
93.
Musto  P , Anderson  KC , Attal  M ,  et al; International Myeloma Working Group.  Second primary malignancies in multiple myeloma: an overview and IMWG consensus.   Ann Oncol. 2017;28(2):228-245. doi:10.1093/annonc/mdw606PubMedGoogle ScholarCrossref
94.
Krishnan  A , Pasquini  MC , Logan  B ,  et al; Blood Marrow Transplant Clinical Trials Network (BMT CTN).  Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial.   Lancet Oncol. 2011;12(13):1195-1203. doi:10.1016/S1470-2045(11)70243-1PubMedGoogle ScholarCrossref
95.
McCarthy  PL , Holstein  SA , Petrucci  MT ,  et al.  Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis.   J Clin Oncol. 2017;35(29):3279-3289. doi:10.1200/JCO.2017.72.6679PubMedGoogle ScholarCrossref
96.
Nooka  AK , Kaufman  JL , Muppidi  S ,  et al.  Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients.   Leukemia. 2014;28(3):690-693. doi:10.1038/leu.2013.335PubMedGoogle ScholarCrossref
97.
Larocca  A , Palumbo  A .  How I treat fragile myeloma patients.   Blood. 2015;126(19):2179-2185. doi:10.1182/blood-2015-05-612960PubMedGoogle ScholarCrossref
98.
Martinez-Lopez  J , Lahuerta  JJ , Pepin  F ,  et al.  Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma.   Blood. 2014;123(20):3073-3079. doi:10.1182/blood-2014-01-550020PubMedGoogle ScholarCrossref
99.
Bahlis  NJ , Dimopoulos  MA , White  DJ ,  et al.  Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study.   Leukemia. 2020;34(7):1875-1884. doi:10.1038/s41375-020-0711-6PubMedGoogle ScholarCrossref
100.
Palumbo  A , Chanan-Khan  A , Weisel  K ,  et al; CASTOR Investigators.  Daratumumab, bortezomib, and dexamethasone for multiple myeloma.   N Engl J Med. 2016;375(8):754-766. doi:10.1056/NEJMoa1606038PubMedGoogle ScholarCrossref
101.
Schey  S , Brown  SR , Tillotson  AL ,  et al; Myeloma UK Early Phase Clinical Trial Network.  Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trial.   Br J Haematol. 2015;170(3):336-348. doi:10.1111/bjh.13435PubMedGoogle ScholarCrossref
102.
Lakshman  A , Singh  PP , Rajkumar  SV ,  et al.  Efficacy of VDT PACE-like regimens in treatment of relapsed/refractory multiple myeloma.   Am J Hematol. 2018;93(2):179-186. doi:10.1002/ajh.24954PubMedGoogle ScholarCrossref
103.
Shah  N , Ahmed  F , Bashir  Q ,  et al.  Durable remission with salvage second autotransplants in patients with multiple myeloma.   Cancer. 2012;118(14):3549-3555. doi:10.1002/cncr.26662PubMedGoogle ScholarCrossref
104.
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.19.02657PubMedGoogle ScholarCrossref
105.
Bjorklund  CC , Kang  J , Amatangelo  M ,  et al.  Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN.   Leukemia. 2020;34(4):1197-1201. doi:10.1038/s41375-019-0620-8PubMedGoogle ScholarCrossref
106.
Morgan  GJ , Child  JA , Gregory  WM ,  et al; National Cancer Research Institute Haematological Oncology Clinical Studies Group.  Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial.   Lancet Oncol. 2011;12(8):743-752. doi:10.1016/S1470-2045(11)70157-7PubMedGoogle ScholarCrossref
107.
Raje  N , Terpos  E , Willenbacher  W ,  et al.  Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study.   Lancet Oncol. 2018;19(3):370-381. doi:10.1016/S1470-2045(18)30072-XPubMedGoogle ScholarCrossref
108.
Mhaskar  R , Kumar  A , Miladinovic  B , Djulbegovic  B .  Bisphosphonates in multiple myeloma: an updated network meta-analysis.   Cochrane Database Syst Rev. 2017;12(12):CD003188. doi:10.1002/14651858.CD003188.pub4PubMedGoogle Scholar
109.
McDonald  RJ , Trout  AT , Gray  LA , Dispenzieri  A , Thielen  KR , Kallmes  DF .  Vertebroplasty in multiple myeloma: outcomes in a large patient series.   AJNR Am J Neuroradiol. 2008;29(4):642-648. doi:10.3174/ajnr.A0918PubMedGoogle ScholarCrossref
110.
Nucci  M , Anaissie  E .  Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents.   Clin Infect Dis. 2009;49(8):1211-1225. doi:10.1086/605664PubMedGoogle ScholarCrossref
111.
Palumbo  A , Rajkumar  SV , San Miguel  JF ,  et al.  International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation.   J Clin Oncol. 2014;32(6):587-600. doi:10.1200/JCO.2013.48.7934PubMedGoogle ScholarCrossref
112.
Drayson  MT , Bowcock  S , Planche  T ,  et al; TEAMM Trial Management Group and Trial Investigators.  Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.   Lancet Oncol. 2019;20(12):1760-1772. doi:10.1016/S1470-2045(19)30506-6PubMedGoogle ScholarCrossref
113.
Tsang  RW , Campbell  BA , Goda  JS ,  et al.  Radiation therapy for solitary plasmacytoma and multiple myeloma: guidelines from the International Lymphoma Radiation Oncology Group.   Int J Radiat Oncol Biol Phys. 2018;101(4):794-808. doi:10.1016/j.ijrobp.2018.05.009PubMedGoogle ScholarCrossref
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