Immunosuppressant Agents
Immunosuppressant agents inhibit key factors in the immune system that are responsible for immune reactions.
Thalidomide (Thalomid)
Thalidomide, when used in combination with dexamethasone, is indicated for the treatment of patients with newly diagnosed multiple myeloma. Thalidomide is an immunomodulatory agent that may suppress excessive production of tumor necrosis factor (TNF)-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration. Because of concerns regarding teratogenicity, thalidomide can only be prescribed by registered physicians and is dispensed by registered pharmacists. Patients must participate in ongoing surveys to receive therapy, and only a 28-d supply can be prescribed at a time.
Lenalidomide (Revlimid)
Lenalidomide is indicated in combination with dexamethasone for multiple myeloma. It is structurally similar to thalidomide. Lenalidomide elicits immunomodulatory and antiangiogenic properties. It inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral blood mononuclear cells.
Pomalidomide (Pomalyst)
Thalidomide analogue indicated in combination with dexamethasone for patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. Also used in combination with elotuzumab and dexamethasone.
Related Questions:
Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011 May 5. 117 (18):4701-5. [Medline].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Multiple Myeloma. Available at https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Version 4.2022 — December 14, 2021; Accessed: March 3, 2022.
Rajkumar SV. Myeloma today: Disease definitions and treatment advances. Am J Hematol. 2016 Jan. 91 (1):90-100. [Medline].
Palumbo A, Rajkumar SV. Treatment of newly diagnosed myeloma. Leukemia. 2009 Mar. 23(3):449-56. [Medline].
Bensinger WI. Role of autologous and allogeneic stem cell transplantation in myeloma. Leukemia. 2009 Mar. 23(3):442-8. [Medline]. [Full Text].
van Nieuwenhuijzen N, Spaan I, Raymakers R, Peperzak V. From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells. Cancer Res. 2018 May 15. 78 (10):2449-2456. [Medline]. [Full Text].
Kuehl WM, Bergsagel PL. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest. 2012 Oct. 122 (10):3456-63. [Medline]. [Full Text].
Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet. 2009 Jul 25. 374(9686):324-39. [Medline].
Ludwig H, Drach J, Graf H, Lang A, Meran JG. Reversal of acute renal failure by bortezomib-based chemotherapy in patients with multiple myeloma. Haematologica. 2007 Oct. 92(10):1411-4. [Medline].
Zucchelli P, Pasquali S, Cagnoli L, Ferrari G. Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney Int. 1988 Jun. 33(6):1175-80. [Medline].
What Causes Multiple Myeloma?. American Cancer Society. Available at https://www.cancer.org/cancer/multiple-myeloma/causes-risks-prevention/what-causes.html. February 28, 2018; Accessed: January 13, 2023.
Koutros S, Baris D, Bell E, Zheng T, Zhang Y, Holford TR, et al. Use of hair colouring products and risk of multiple myeloma among US women. Occup Environ Med. 2009 Jan. 66 (1):68-70. [Medline]. [Full Text].
Wadhera RK, Kyle RA, Larson DR, et al. Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma. Blood. 2011 Sep 15. 118(11):2985-7. [Medline].
Yiin JH, Anderson JL, Daniels RD, Seel EA, Fleming DA, Waters KM, et al. A nested case-control study of multiple myeloma risk and uranium exposure among workers at the Oak Ridge Gaseous Diffusion Plant. Radiat Res. 2009 Jun. 171(6):637-45. [Medline].
Caers J, Vande broek I, De Raeve H, Michaux L, Trullemans F, Schots R, et al. Multiple myeloma--an update on diagnosis and treatment. Eur J Haematol. 2008 Nov. 81(5):329-43. [Medline].
Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan. 23(1):3-9. [Medline]. [Full Text].
Key Statistics About Multiple Myeloma. American Cancer Society. Available at https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. January 12, 2023; Accessed: January 13, 2023.
Surveillance, Epidemiology, and End Results Program. SEER Stat Fact Sheets: Myeloma. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed: January 13, 2023.
Ailawadhi S, Aldoss IT, Yang D, Razavi P, Cozen W, Sher T, et al. Outcome disparities in multiple myeloma: a SEER-based comparative analysis of ethnic subgroups. Br J Haematol. 2012 Apr 26. [Medline].
Ludwig H, Durie BG, Bolejack V, Turesson I, Kyle RA, Blade J, et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood. 2008 Apr 15. 111(8):4039-47. [Medline].
Bataille R, Boccadoro M, Klein B, Durie B, Pileri A. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood. 1992 Aug 1. 80(3):733-7. [Medline].
Augustson BM, Begum G, Dunn JA, Barth NJ, Davies F, Morgan G, et al. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party. J Clin Oncol. 2005 Dec 20. 23(36):9219-26. [Medline].
Blimark C, Holmberg E, Mellqvist UH, Landgren O, Björkholm M, Hultcrantz M, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015 Jan. 100(1):107-13. [Medline]. [Full Text].
Bladé J, Fernández-Llama P, Bosch F, Montolíu J, Lens XM, Montoto S, et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med. 1998 Sep 28. 158(17):1889-93. [Medline].
Dimopoulos M, Terpos E, Comenzo RL, Tosi P, Beksac M, Sezer O, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia. 2009 Sep. 23(9):1545-56. [Medline].
Hung GU, Tsai CC, Tsai SC, Lin WY. Comparison of Tc-99m sestamibi and F-18 FDG-PET in the assessment of multiple myeloma. Anticancer Res. 2005 Nov-Dec. 25(6C):4737-41. [Medline].
Shortt CP, Gleeson TG, Breen KA, McHugh J, O'Connell MJ, O'Gorman PJ, et al. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity. AJR Am J Roentgenol. 2009 Apr. 192(4):980-6. [Medline].
Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011 Dec 1. 118(23):5989-95. [Medline].
Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep. 36(3):842-54. [Medline].
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20. 23(15):3412-20. [Medline].
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 Sep 10. 33 (26):2863-9. [Medline]. [Full Text].
Dimopoulos MA, Moulopoulos A, Smith T, Delasalle KB, Alexanian R. Risk of disease progression in asymptomatic multiple myeloma. Am J Med. 1993 Jan. 94(1):57-61. [Medline].
He Y, Wheatley K, Clark O, Glasmacher A, Ross H, Djulbegovic B. Early versus deferred treatment for early stage multiple myeloma. Cochrane Database Syst Rev. 2003. CD004023. [Medline].
Munshi NC, Anderson KC, Bergsagel PL, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. 2011 May 5. 117(18):4696-700. [Medline].
Klein U, Jauch A, Hielscher T, et al. Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer. 2011 May 15. 117(10):2136-44. [Medline].
Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012 Jan 26. 119(4):940-8. [Medline].
Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013 Aug 1. 369(5):438-47. [Medline].
Drug Shows Promise in Slowing Progression of Smoldering Myeloma to Cancer. National Cancer Institute. Available at https://www.cancer.gov/news-events/cancer-currents-blog/2019/lenalidomide-slows-progression-smoldering-myeloma. June 7, 2019; Accessed: March 5, 2020.
Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore DF Sr, Whittenberger BF, et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood. 2010 Dec 23. 116(26):5838-41. [Medline]. [Full Text].
Nelson R. High-risk smoldering myeloma benefits from early treatment. Medscape Medical News. August 1, 2013. [Full Text].
Mateos MV, Hernandez MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013 Aug 1. 369(5):438-47. [Medline].
Morgan GJ, Child JA, Gregory WM, et al. 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 Aug. 12(8):743-52. [Medline].
Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med. 1996 Feb 22. 334(8):488-93. [Medline].
[Guideline] Anderson K, Ismaila N, Kyle RA. Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. J Oncol Pract. 2018 Apr. 14 (4):266-269. [Medline]. [Full Text].
Mikkilineni L, Kochenderfer JN. CAR T cell therapies for patients with multiple myeloma. Nat Rev Clin Oncol. 2021 Feb. 18 (2):71-84. [Medline].
Dhakal B, Hari PN, Usmani SZ, Hamadani M. Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges. Bone Marrow Transplant. 2021 Jan. 56 (1):9-19. [Medline].
[Guideline] Terpos E, et al; Bone Working Group of the International Myeloma Working Group. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021 Feb 2. [Medline]. [Full Text].
Zonder JA, Crowley J, Hussein MA, et al. Superiority of lenalidomide (Len) plus high-dose dexamethasone (HD) compared to HD alone as treatment of newly-diagnosed multiple myeloma (NDMM): results of the randomized, double-blinded, placebo-controlled SWOG trial S0232 [abstract 77]. Blood. 2007. 110:32a. [Full Text].
Lokhorst HM, Sonneveld P, Cornelissen JJ, Joosten P, van Marwijk Kooy M, Meinema J, et al. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant. 1999 Feb. 23(4):317-22. [Medline].
Zervas K, Mihou D, Katodritou E, Pouli A, Mitsouli CH, Anagnostopoulos A, et al. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol. 2007 Aug. 18(8):1369-75. [Medline].
Lenalidomide Improves Survival in Newly-Diagnosed Multiple Myeloma. Medscape Medical News. Available at https://www.medscape.com/viewarticle/807706. Accessed: July 23, 2013.
Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. 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 Jan. 11(1):29-37. [Medline].
Niesvizky R, Jayabalan DS, Christos PJ, Furst JR, Naib T, Ely S, et al. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood. 2008 Feb 1. 111(3):1101-9. [Medline].
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26. 348(26):2609-17. [Medline].
Harousseau JL, Mathiot C, Attal M, et al. VELCADE/dexamethasone (Vel/D) versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): updated results of the IFM 2005/01 trial [abstract 450]. Blood. 2007. 110:139a. [Full Text].
Cavo M, Patriarca F, Tacchetti P, et al. . Bortezomib (Velcade[R])-thalidomide-dexamethasone (VTD) vs thalidomide-dexamethasone (TD) in preparation for autologous stem-cell (SC) transplantation (ASCT) in newly diagnosed multiple myeloma (MM) [abstract 73]. Blood. 2007. 110:30a. [Full Text].
Sher T, Ailawadhi S, Miller KC, et al. A steroid-independent regimen of bortezomib, liposomal doxorubicin and thalidomide demonstrate high response rates in newly diagnosed multiple myeloma patients. Br J Haematol. 2011 Jul. 154(1):104-10. [Medline].
Harousseau JL, Palumbo A, Richardson PG, Schlag R, Dimopoulos MA, Shpilberg O, et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood. 2010 Nov 11. 116(19):3743-50. [Medline].
Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011 May. 12(5):431-40. [Medline].
Mateos MV, Gutierrez NC, Martin-Ramos ML, et al. Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance. Blood. 2011 Oct 27. 118(17):4547-53. [Medline].
Moreau, Philippe, 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 Jul 6. 394 (10192):29-38. [Medline].
Sonneveld P, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Nov 22. JCO2102734. [Medline].
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Overall Survival With Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2023 Jan 4. JCO2200940. [Medline]. [Full Text].
Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007 Jan. 21(1):151-7. [Medline].
Sagaster V, Ludwig H, Kaufmann H, Odelga V, Zojer N, Ackermann J, et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia. 2007 Jan. 21(1):164-8. [Medline].
Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol. 1998 Dec. 16(12):3832-42. [Medline].
Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007 Oct 6. 370(9594):1209-18. [Medline].
Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009 Aug 1. 27(22):3664-70. [Medline].
Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Björkstrand B, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010 Sep 2. 116(9):1405-12. [Medline].
Fayers PM, Palumbo A, Hulin C, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011 Aug 4. 118(5):1239-47. [Medline].
Zweegman S, van der Holt B, Mellqvist UH, et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016 Mar 3. 127 (9):1109-16. [Medline]. [Full Text].
Gay F, Larocca A, Wijermans P, et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2011 Mar 17. 117(11):3025-31. [Medline].
Mateos MV, et al, for the ALCYONE Trial Investigators. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2017 Dec 12. [Medline]. [Full Text].
Facon T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019 May 30. 380 (22):2104-2115. [Medline]. [Full Text].
Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009 Apr 10. 27(11):1788-93. [Medline].
Lokhorst HM, van der Holt B, Zweegman S, et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11. 115(6):1113-20. [Medline].
Morgan GJ, Gregory WM, Davies FE, et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012 Jan 5. 119(1):7-15. [Medline].
McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10. 366(19):1770-81. [Medline]. [Full Text].
Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10. 366(19):1782-91. [Medline].
Yang B, Yu RL, Chi XH, Lu XC. Lenalidomide treatment for multiple myeloma: systematic review and meta-analysis of randomized controlled trials. PLoS One. 2013. 8 (5):e64354. [Medline]. [Full Text].
Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20. 30(24):2946-55. [Medline].
Palumbo A, Hajek R, Delforge M, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10. 366(19):1759-69. [Medline].
Palumbo A, Mina R. Part II: role of maintenance therapy in transplant-ineligible patients. J Natl Compr Canc Netw. 2013 Jan 1. 11(1):43-9. [Medline].
FDA approves carfilzomib and daratumumab with dexamethasone for multiple myeloma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-carfilzomib-and-daratumumab-dexamethasone-multiple-myeloma. August 21, 2020; Accessed: September 2, 2020.
San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, 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 Oct. 15(11):1195-206. [Medline].
Kyprolis (carfilzomib) [package insert]. South San Francisco, CA: Onyx Pharmaceuticals. July 2012. Available at [Full Text].
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8. 372 (2):142-52. [Medline]. [Full Text].
Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. 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 Jan. 17 (1):27-38. [Medline].
Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, 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 Oct. 18 (10):1327-1337. [Medline].
Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9. 387 (10027):1551-60. [Medline]. [Full Text].
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24. 373 (13):1207-19. [Medline].
Moreau P, et al, for the TOURMALINE-MM1 Study Group. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Apr 28. 374 (17):1621-34. [Medline]. [Full Text].
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015 Aug 13. 373 (7):621-31. [Medline].
Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018 Nov 8. 379 (19):1811-1822. [Medline].
Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, 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. Lancet. 2019 Dec 7. 394 (10214):2096-2107. [Medline].
FDA approves isatuximab-irfc for multiple myeloma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-isatuximab-irfc-multiple-myeloma. March 31, 2021; Accessed: April 15, 2021.
Kumar S, Witzig TE, Rajkumar SV. Thalidomid: current role in the treatment of non-plasma cell malignancies. J Clin Oncol. 2004 Jun 15. 22(12):2477-88. [Medline].
Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22. 357(21):2133-42. [Medline].
Lacy MQ, Allred JB, Gertz MA, et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011 Sep 15. 118(11):2970-5. [Medline].
Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, et al. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. Blood. 2013 Jan 14. [Medline].
Chustecka Z, Mulcahy N. FDA Approves Pomalidomide for Multiple Myeloma. Medscape Medical News. Available at https://www.medscape.com/viewarticle/779048. February 8, 2013; Accessed: January 11, 2018.
Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, 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 Sep 2. [Medline].
Ajai C, Vogl DT, et al. Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta-Refractory MM. Blood 2018 132:598. [Full Text].
Xpovio (selinexor) [package insert]. Newton, MA: Karyopharm Therapeutics, Inc. July 2019. Available at [Full Text].
FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma. August 5, 2020; Accessed: November 9, 2022.
Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 Aug 11. 387 (6):495-505. [Medline].
Moreau P, Hullin C, Garban F, Yakoub-Agha I, Benboubker L, Attal M, et al. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol. Blood. 2006 Jan 1. 107(1):397-403. [Medline].
Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007 Jun 10. 25(17):2434-41. [Medline].
Barlogie B, Attal M, Crowley J, van Rhee F, Szymonifka J, Moreau P, et al. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the intergroupe francophone du myelome, southwest oncology group, and university of arkansas for medical sciences. J Clin Oncol. 2010 Mar 1. 28(7):1209-14. [Medline]. [Full Text].
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996 Jul 11. 335(2):91-7. [Medline].
Gerull S, Goerner M, Benner A, Hegenbart U, Klein U, Schaefer H, et al. Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma. Bone Marrow Transplant. 2005 Dec. 36(11):963-9. [Medline].
Vesole DH, Zhang L, Flomenberg N, Greipp PR, Lazarus HM, Huff CA. A Phase II trial of autologous stem cell transplantation followed by mini-allogeneic stem cell transplantation for the treatment of multiple myeloma: an analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97. Biol Blood Marrow Transplant. 2009 Jan. 15(1):83-91. [Medline].
Bruno B, Rotta M, Patriarca F, Mattei D, Allione B, Carnevale-Schianca F, et al. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood. 2009 Apr 2. 113(14):3375-82. [Medline]. [Full Text].
Rotta M, Storer BE, Sahebi F, Shizuru JA, Bruno B, Lange T, et al. Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting. Blood. 2009 Apr 2. 113(14):3383-91. [Medline]. [Full Text].
Moreau P, Attal M, Pégourié B, et al. Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial. Blood. 2011 Mar 17. 117(11):3041-3044. [Medline].
Harousseau JL, Attal M, Avet-Loiseau H, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20. 28(30):4621-9. [Medline].
Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18. 376(9758):2075-85. [Medline].
Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D, et al. Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012 May 14. [Medline].
FDA Approves First Cell-Based Gene Therapy for Adult Patients with Multiple Myeloma. Food and Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-adult-patients-multiple-myeloma. March 21, 2021; Accessed: April 5, 2021.
Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Feb 25. 384 (8):705-716. [Medline].
Carvykti (ciltacabtagene autoleucel) [package insert]. Horsham, PA: Janssen Biotech, Inc. March 2022. Available at [Full Text].
Martin T, Usmani SZ, Berdeja JG, Jakubowiak A, Agha M, Cohen AD, et al. Updated results from CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma (abstract #549). Presented at the 64th American Society of Hematology (ASH) Annual Meeting. American Society of Hematology. Available at https://ash.confex.com/ash/2021/webprogram/Paper146060.html. December 12, 2021; Accessed: March 3, 2022.
Cooper MR, Dear K, McIntyre OR, Ozer H, Ellerton J, Canellos G, et al. A randomized clinical trial comparing melphalan/prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study. J Clin Oncol. 1993 Jan. 11(1):155-60. [Medline].
Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11. 376(9757):1989-99. [Medline].
Terpos E, Roodman GD, Willenbacher W, Shimizu K, Garcia-Sanz R, Durie B, et al. Comparison of denosumab (DMB) with zoledronic acid (ZA) for the treatment of bone disease in patients with newly diagnosed multiple myeloma; an international, randomized, double blind trial (oral presentation S782). Presented at the 22nd Annual Congress of the European Hematology Association, Madrid Spain. 2017 June 25. [Full Text].
[Guideline] Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014 Oct. 72(10):1938-56. [Medline]. [Full Text].
Djulbegovic B, Wheatley K, Ross J, Clark O, Bos G, Goldschmidt H, et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev. 2001. CD003188. [Medline].
Bloomfield DJ. Should bisphosphonates be part of the standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review. J Clin Oncol. 1998 Mar. 16(3):1218-25. [Medline].
Ludwig H, Fritz E, Kotzmann H, Höcker P, Gisslinger H, Barnas U. Erythropoietin treatment of anemia associated with multiple myeloma. N Engl J Med. 1990 Jun 14. 322(24):1693-9. [Medline].
Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, et al. A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess. 2007 Apr. 11(13):1-202, iii-iv. [Medline].
Parikh GC, Amjad AI, Saliba RM, Kazmi SM, Khan ZU, Lahoti A, et al. Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant. 2009 Jul. 15(7):812-6. [Medline].
[Guideline] Terpos E, Kleber M, Engelhardt M, et al; European Myeloma Network. European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications. Haematologica. 2015 Oct. 100 (10):1254-66. [Medline]. [Full Text].
Golombick T, Diamond TH, Manoharan A, Ramakrishna R. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study. Am J Hematol. 2012 May. 87(5):455-60. [Medline].
Chang ET, Canchola AJ, Cockburn M, et al. Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood. 2011 Aug 11. 118(6):1591-9. [Medline]. [Full Text].
[Guideline] Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov. 15 (12):e538-48. [Medline].
[Guideline] Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Hemasphere. 2021 Feb. 5 (2):e528. [Medline]. [Full Text].
[Guideline] 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 Sep 10. 33 (26):2863-9. [Medline]. [Full Text].
[Guideline] Bohlius J, Bohlke K, Castelli R, Djulbegovic B, Lustberg MB, Martino M, et al. Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update. J Clin Oncol. 2019 May 20. 37 (15):1336-1351. [Medline]. [Full Text].
[Guideline] National Comprehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf. Version 1.2020 — April 16, 2020; Accessed: February 3, 2021.
Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008 Feb. 22 (2):414-23. [Medline]. [Full Text].
Ludwig H, Boccadoro M, Moreau P, et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2021 Jan. 35 (1):31-44. [Medline]. [Full Text].
Lonial S, Lee HC, Badros A, Trudel S, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020 Feb. 21 (2):207-221. [Medline].
Adding Isatuximab to Pomalidomide and Low-Dose Dexamethasone Improves PFS in Relapsed and Refractory Multiple Myeloma. ESMO. Available at https://www.esmo.org/oncology-news/adding-isatuximab-to-pomalidomide-and-low-dose-dexamethasone-improves-pfs-in-relapsed-and-refractory-multiple-myeloma. November 20, 2019; Accessed: February 3, 2021.
van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021 Jan 30. 397 (10272):410-427. [Medline].
Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1. 28(13):2259-66. [Medline].
Palumbo A, Falco P, Falcone A, Benevolo G, Canepa L, Gay F, et al. Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. Clin Lymphoma Myeloma. 2009 Apr. 9(2):145-50. [Medline].
Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15. 108(10):3289-94. [Medline].
Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood. 2008 Oct 15. 112(8):3115-21. [Medline]. [Full Text].
Ludwig H, Hajek R, Tóthová E, Drach J, Adam Z, Labar B, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood. 2009 Apr 9. 113(15):3435-42. [Medline].
van Rhee F, Dhodapkar M, Shaughnessy JD Jr, Anaissie E, Siegel D, Hoering A, et al. First thalidomide clinical trial in multiple myeloma: a decade. Blood. 2008 Aug 15. 112(4):1035-8. [Medline]. [Full Text].
[Guideline] Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2017 Apr 27. [Medline]. [Full Text].
Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4. 118(5):1231-8. [Medline]. [Full Text].
Vickrey E, Allen S, Mehta J, Singhal S. Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. 2009 Jan 1. 115(1):229-32. [Medline].
Petrucci MT, Giraldo P, Corradini P, et al. A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma. Br J Haematol. 2013 Jan 7. [Medline].
Rodon P. Management and treatment of multiple myeloma in elderly patients. Ann Long-Term Care. 2002. 10:20-7.
Palumbo A, Cavo M, Bringhen S, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10. 29(8):986-93. [Medline].
Jackson GH, Morgan GJ, Davies FE, Wu P, Gregory WM, Bell SE, et al. Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results. Br J Haematol. 2014 Jul. 166(1):109-17. [Medline].
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Amyloidosis infiltrating the tongue in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Radiograph of the skull demonstrating a typical lytic lesion in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Bone marrow aspirate demonstrating plasma cells of multiple myeloma. Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone (or halo). All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Bone marrow biopsy demonstrating sheets of malignant plasma cells in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Dhaval Shah, MD Helen F Graham Cancer Center and Research Institute
Dhaval Shah, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College
Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology
Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences
Disclosure: Nothing to disclose.