nach oben

Targeted Oncology

Erschienen in:

30.06.2022 | Review Article

What’s Old is New: The Past, Present and Future Role of Thalidomide in the Modern-Day Management of Multiple Myeloma

verfasst von: Bruno Almeida Costa, Tarek H. Mouhieddine, Joshua Richter

Erschienen in: Targeted Oncology | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Abstract

Immunomodulatory drugs (IMiDs) have become an integral part of therapy for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM). IMiDs bind to cereblon, leading to the degradation of proteins involved in B-cell survival and proliferation. Thalidomide, a first-generation IMiD, has little to no myelosuppressive potential, negligible renal clearance, and long-proven anti-myeloma activity. However, thalidomide’s adverse effects (e.g., somnolence, constipation, and peripheral neuropathy) and the advent of more potent therapeutic options has led to the drug being less frequently used in many countries, including the US and Canada. Newer-generation IMiDs, such as lenalidomide and pomalidomide, are utilized far more frequently. In numerous previous trials, salvage therapy with thalidomide (50–200 mg/day) plus corticosteroids (with or without selected cytotoxic or targeted agents) has been shown to be effective and well-tolerated in the RRMM setting. Hence, thalidomide-based regimens remain important alternatives for heavily pretreated patients, especially for those who have no access to novel therapies and/or are not eligible for their use (due to renal failure, high-grade myelosuppression, or significant comorbidities). Ongoing and future trials may provide further insights into the current role of thalidomide, especially by comparing thalidomide-containing regimens with protocols based on newer-generation IMiDs and by investigating thalidomide’s association with novel therapies (e.g., antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells).

van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397(10272):410–27. https://doi.org/10.1016/S0140-6736(21)00135-5.CrossRefPubMed

Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60. https://doi.org/10.1056/NEJMra1011442.CrossRefPubMed

Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48. https://doi.org/10.1016/S1470-2045(14)70442-5.CrossRefPubMed

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.CrossRefPubMed

Cowan AJ, Green DJ, Kwok M, Lee S, Coffey DG, Holmberg LA, et al. Diagnosis and management of multiple myeloma: a review. JAMA. 2022;327(5):464–77. https://doi.org/10.1001/jama.2022.0003.CrossRefPubMed

Therneau TM, Kyle RA, Melton LJ 3rd, Larson DR, Benson JT, Colby CL, et al. Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition. Mayo Clin Proc. 2012;87(11):1071–9. https://doi.org/10.1016/j.mayocp.2012.06.014.CrossRefPubMedPubMedCentral

Solly S. Remarks on the pathology of mollities ossium; with cases. Med Chir Trans. 1844;27:435–98. https://doi.org/10.1177/095952874402700129.CrossRefPubMedPubMedCentral

Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–16. https://doi.org/10.1056/NEJMoa2024850.CrossRefPubMed

Morgan GJ, Boyle EM, Davies FE. From bench to bedside: the evolution of genomics and its implications for the current and future management of multiple myeloma. Cancer J. 2021;27(3):213–21. https://doi.org/10.1097/PPO.0000000000000523.CrossRefPubMed

10.

Mateos MV, Ludwig H, Bazarbachi A, Beksac M, Bladé J, Boccadoro M, et al. Insights on multiple myeloma treatment strategies. Hemasphere. 2018;3(1): e163. https://doi.org/10.1097/HS9.0000000000000163.CrossRefPubMedPubMedCentral

11.

Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548–67. https://doi.org/10.1002/ajh.25791.CrossRefPubMed

12.

Schavgoulidze A, Cazaubiel T, Perrot A, Avet-Loiseau H, Corre J. Multiple myeloma: heterogeneous in every way. Cancers (Basel). 2021;13(6):1285. https://doi.org/10.3390/cancers13061285.CrossRefPubMedPubMedCentral

13.

Ackley J, Ochoa MA, Ghoshal D, Roy K, Lonial S, Boise LH. Keeping myeloma in check: the past, present and future of immunotherapy in multiple myeloma. Cancers (Basel). 2021;13(19):4787. https://doi.org/10.3390/cancers13194787.CrossRefPubMedPubMedCentral

14.

Ludwig H. Myeloma research on the move. Blood Cancer J. 2021;11(9):155. https://doi.org/10.1038/s41408-021-00550-z.CrossRefPubMedPubMedCentral

15.

Theodoropoulos N, Lancman G, Chari A. Targeting nuclear export proteins in multiple myeloma therapy. Target Oncol. 2020;15(6):697–708. https://doi.org/10.1007/s11523-020-00758-2.CrossRefPubMedPubMedCentral

16.

Sanchez L, Dardac A, Madduri D, Richard S, Richter J. B-cell maturation antigen (BCMA) in multiple myeloma: the new frontier of targeted therapies. Ther Adv Hematol. 2021;12:2040620721989585. https://doi.org/10.1177/2040620721989585.CrossRefPubMedPubMedCentral

17.

Legarda MA, Cejalvo MJ, de la Rubia J. Recent advances in the treatment of patients with multiple myeloma. Cancers (Basel). 2020;12(12):3576. https://doi.org/10.3390/cancers12123576.CrossRefPubMedCentral

18.

National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. SEER cancer statistics review 1973–1994. 1997. Available at: https://seer.cancer.gov/archive/csr/1973_1994/myeloma.pdf. Accessed 6 Feb 2022.

19.

National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Cancer stat facts: myeloma. 2021. Available at: https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed 6 Feb 2022.

20.

Luo J, Gagne JJ, Landon J, Avorn J, Kesselheim AS. Comparative effectiveness and safety of thalidomide and lenalidomide in patients with multiple myeloma in the United States of America: a population-based cohort study. Eur J Cancer. 2017;70:22–33. https://doi.org/10.1016/j.ejca.2016.10.018.CrossRefPubMed

21.

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. Ann Oncol. 2021;32(3):309–22. https://doi.org/10.1016/j.annonc.2020.11.014.CrossRefPubMed

22.

Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, 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. https://doi.org/10.1016/S0140-6736(19)31240-1.CrossRefPubMed

23.

National Comprehensive Cancer Network (NCCN). NCCN guidelines: multiple myeloma, version 5.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. 2022. Accessed 15 Mar 2022.

24.

Thakurta A, Pierceall WE, Amatangelo MD, Flynt E, Agarwal A. Developing next generation immunomodulatory drugs and their combinations in multiple myeloma. Oncotarget. 2021;12(15):1555–63. https://doi.org/10.18632/oncotarget.27973.CrossRefPubMedPubMedCentral

25.

Harousseau JL. Thalidomide in multiple myeloma: past, present and future. Future Oncol. 2006;2(5):577–89. https://doi.org/10.2217/14796694.2.5.577.CrossRefPubMed

26.

Tseng S, Pak G, Washenik K, Pomeranz MK, Shupack JL. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. 1996;35(6):969–79. https://doi.org/10.1016/s0190-9622(96)90122-x.CrossRefPubMed

27.

Ribatti D, Vacca A. Therapeutic renaissance of thalidomide in the treatment of haematological malignancies. Leukemia. 2005;19(9):1525–31. https://doi.org/10.1038/sj.leu.2403852.CrossRefPubMed

28.

Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004;4(4):314–22. https://doi.org/10.1038/nrc1323.CrossRefPubMed

29.

Brent RL. Drug testing in animals for teratogenic effects. Thalidomide in the pregnant rat. J Pediatr. 1964;64:762–70. https://doi.org/10.1016/s0022-3476(64)80626-0.CrossRefPubMed

30.

Rehman W, Arfons LM, Lazarus HM. The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development. Ther Adv Hematol. 2011;2(5):291–308. https://doi.org/10.1177/2040620711413165.CrossRefPubMedPubMedCentral

31.

Ances BM. New concerns about thalidomide. Obstet Gynecol. 2002;99(1):125–8. https://doi.org/10.1016/s0029-7844(01)01662-3.CrossRefPubMed

32.

Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today. 2015;105(2):140–56. https://doi.org/10.1002/bdrc.21096.CrossRefPubMedPubMedCentral

33.

Olson KB, Hall TC, Horton J, Khung CL, Hosley HF. Thalidomide (N-phthaloylglutamimide) in the treatment of advanced cancer. Clin Pharmacol Ther. 1965;6:292–7. https://doi.org/10.1002/cpt196563292.CrossRefPubMed

34.

Grabstald H, Golbey R. Clinical experiences with thalidomide in patients with cancer. Clin Pharmacol Ther. 1965;6:298–302. https://doi.org/10.1002/cpt196563298.CrossRefPubMed

35.

Sheskin J. Thalidomide in the treatment of lepra reactions. Clin Pharmacol Ther. 1965;6:303–6. https://doi.org/10.1002/cpt196563303.CrossRefPubMed

36.

Jacobson JM. Thalidomide: a remarkable comeback. Expert Opin Pharmacother. 2000;1(4):849–63. https://doi.org/10.1517/14656566.1.4.849.CrossRefPubMed

37.

Iyer CG, Languillon J, Ramanujam K, Tarabini-Castellani G, De las Aguas JT, Bechelli LM, et al. WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients. Bull World Health Organ. 1971;45(6):719–32.PubMedPubMedCentral

38.

Lenardo TM, Calabrese LH. The role of thalidomide in the treatment of rheumatic disease. J Clin Rheumatol. 2000;6(1):19–26. https://doi.org/10.1097/00124743-200002000-00003.CrossRefPubMed

39.

Wines NY, Cooper AJ, Wines MP. Thalidomide in dermatology. Australas J Dermatol. 2002;43(4):229–40. https://doi.org/10.1046/j.1440-0960.2002.00608.x.CrossRefPubMed

40.

Kim JH, Scialli AR. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol Sci. 2011;122(1):1–6. https://doi.org/10.1093/toxsci/kfr088.CrossRefPubMed

41.

Matthews SJ, McCoy C. Thalidomide: a review of approved and investigational uses. Clin Ther. 2003;25(2):342–95. https://doi.org/10.1016/s0149-2918(03)80085-1.CrossRefPubMed

42.

Calabrese L, Resztak K. Thalidomide revisited: pharmacology and clinical applications. Expert Opin Investig Drugs. 1998;7(12):2043–60. https://doi.org/10.1517/13543784.7.12.2043.CrossRefPubMed

43.

D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA. 1994;91(9):4082–5. https://doi.org/10.1073/pnas.91.9.4082.CrossRefPubMedPubMedCentral

44.

Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1(1):27–31. https://doi.org/10.1038/nm0195-27.CrossRefPubMed

45.

Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F, et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol. 1994;87(3):503–8. https://doi.org/10.1111/j.1365-2141.1994.tb08304.x.CrossRefPubMed

46.

Vacca A, Ribatti D, Roncali L, Dammacco F. Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical studies. Leuk Lymphoma. 1995;20(1–2):27–38. https://doi.org/10.3109/10428199509054750.CrossRefPubMed

47.

Amare GG, Meharie BG, Belayneh YM. A drug repositioning success: the repositioned therapeutic applications and mechanisms of action of thalidomide. J Oncol Pharm Pract. 2021;27(3):673–8. https://doi.org/10.1177/1078155220975825.CrossRefPubMed

48.

Palumbo A, Palladino C. Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance. Ther Adv Drug Saf. 2012;3(5):255–66. https://doi.org/10.1177/2042098612452291.CrossRefPubMedPubMedCentral

49.

Kazandjian D, Landgren O. A look backward and forward in the regulatory and treatment history of multiple myeloma: approval of novel-novel agents, new drug development, and longer patient survival. Semin Oncol. 2016;43(6):682–9. https://doi.org/10.1053/j.seminoncol.2016.10.008.CrossRefPubMedPubMedCentral

50.

Kawano Y, Moschetta M, Manier S, Glavey S, Görgün GT, Roccaro AM, et al. Targeting the bone marrow microenvironment in multiple myeloma. Immunol Rev. 2015;263(1):160–72. https://doi.org/10.1111/imr.12233.CrossRefPubMed

51.

Rajkumar SV, Mesa RA, Fonseca R, Schroeder G, Plevak MF, Dispenzieri A, et al. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res. 2002;8(7):2210–6.PubMed

52.

Rajkumar SV, Witzig TE. A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple myeloma. Cancer Treat Rev. 2000;26(5):351–62. https://doi.org/10.1053/ctrv.2000.0188.CrossRefPubMed

53.

Jakob C, Sterz J, Zavrski I, Heider U, Kleeberg L, Fleissner C, et al. Angiogenesis in multiple myeloma. Eur J Cancer. 2006;42(11):1581–90. https://doi.org/10.1016/j.ejca.2006.02.017.CrossRefPubMed

54.

Moser-Katz T, Joseph NS, Dhodapkar MV, Lee KP, Boise LH. Game of bones: how myeloma manipulates its microenvironment. Front Oncol. 2021;10: 625199. https://doi.org/10.3389/fonc.2020.625199.CrossRefPubMedPubMedCentral

55.

Podar K, Anderson KC. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood. 2005;105(4):1383–95. https://doi.org/10.1182/blood-2004-07-2909.CrossRefPubMed

56.

Rajkumar SV, Leong T, Roche PC, Fonseca R, Dispenzieri A, Lacy MQ, et al. Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin Cancer Res. 2000;6(8):3111–6.PubMed

57.

Sezer O, Niemöller K, Eucker J, Jakob C, Kaufmann O, Zavrski I, et al. Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Ann Hematol. 2000;79(10):574–7. https://doi.org/10.1007/s002770000236.CrossRefPubMed

58.

Lee N, Lee H, Moon SY, Sohn JY, Hwang SM, Yoon OJ, et al. Adverse prognostic impact of bone marrow microvessel density in multiple myeloma. Ann Lab Med. 2015;35(6):563–9. https://doi.org/10.3343/alm.2015.35.6.563.CrossRefPubMedPubMedCentral

59.

Kumar S, Gertz MA, Dispenzieri A, Lacy MQ, Wellik LA, Fonseca R, et al. Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy. Bone Marrow Transplant. 2004;34(3):235–9. https://doi.org/10.1038/sj.bmt.1704555.CrossRefPubMed

60.

Kumar S, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Wellik L, et al. Prognostic value of angiogenesis in solitary bone plasmacytoma. Blood. 2003;101(5):1715–7. https://doi.org/10.1182/blood-2002-08-2441.CrossRefPubMed

61.

Kenyon BM, Browne F, D’Amato RJ. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res. 1997;64(6):971–8. https://doi.org/10.1006/exer.1997.0292.CrossRefPubMed

62.

Tamilarasan KP, Kolluru GK, Rajaram M, Indhumathy M, Saranya R, Chatterjee S. Thalidomide attenuates nitric oxide mediated angiogenesis by blocking migration of endothelial cells. BMC Cell Biol. 2006;7:17. https://doi.org/10.1186/1471-2121-7-17.CrossRefPubMedPubMedCentral

63.

Majumder S, Rajaram M, Muley A, Reddy HS, Tamilarasan KP, Kolluru GK, et al. Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase. Br J Pharmacol. 2009;158(7):1720–34. https://doi.org/10.1111/j.1476-5381.2009.00446.x.CrossRefPubMedPubMedCentral

64.

Vacca A, Scavelli C, Montefusco V, Di Pietro G, Neri A, Mattioli M, et al. Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma. J Clin Oncol. 2005;23(23):5334–46. https://doi.org/10.1200/JCO.2005.03.723.CrossRefPubMed

65.

Ria R, Melaccio A, Racanelli V, Vacca A. Anti-VEGF drugs in the treatment of multiple myeloma patients. J Clin Med. 2020;9(6):1765. https://doi.org/10.3390/jcm9061765.CrossRefPubMedCentral

66.

Ribatti D, Vacca A. New insights in anti-angiogenesis in multiple myeloma. Int J Mol Sci. 2018;19(7):2031. https://doi.org/10.3390/ijms19072031.CrossRefPubMedCentral

67.

Kumar S, Witzig TE, Dispenzieri A, Lacy MQ, Wellik LE, Fonseca R, et al. Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma. Leukemia. 2004;18(3):624–7. https://doi.org/10.1038/sj.leu.2403285.CrossRefPubMed

68.

Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99(12):4525–30. https://doi.org/10.1182/blood.v99.12.4525.CrossRefPubMed

69.

Al-Hujaily EM, Oldham RA, Hari P, Medin JA. Development of novel immunotherapies for multiple myeloma. Int J Mol Sci. 2016;17(9):1506. https://doi.org/10.3390/ijms17091506.CrossRefPubMedCentral

70.

Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24(1):22–32. https://doi.org/10.1038/leu.2009.236.CrossRefPubMed

71.

D’Souza C, Prince HM, Neeson PJ. Understanding the role of T-cells in the antimyeloma effect of immunomodulatory drugs. Front Immunol. 2021;12: 632399. https://doi.org/10.3389/fimmu.2021.632399.CrossRefPubMedPubMedCentral

72.

Haslett PA, Corral LG, Albert M, Kaplan G. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med. 1998;187(11):1885–92. https://doi.org/10.1084/jem.187.11.1885.CrossRefPubMedPubMedCentral

73.

LeBlanc R, Hideshima T, Catley LP, Shringarpure R, Burger R, Mitsiades N, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood. 2004;103(5):1787–90. https://doi.org/10.1182/blood-2003-02-0361.CrossRefPubMed

74.

Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai YT, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98(1):210–6. https://doi.org/10.1182/blood.v98.1.210.CrossRefPubMed

75.

Fritz E, Ludwig H. Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients. Ann Oncol. 2000;11(11):1427–36. https://doi.org/10.1023/a:1026548226770.CrossRefPubMed

76.

Ito T, Handa H. Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs. Int J Hematol. 2016;104(3):293–9. https://doi.org/10.1007/s12185-016-2073-4.CrossRefPubMed

77.

Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327(5971):1345–50. https://doi.org/10.1126/science.1177319.CrossRefPubMed

78.

Zhu YX, Braggio E, Shi CX, Bruins LA, Schmidt JE, Van Wier S, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118(18):4771–9. https://doi.org/10.1182/blood-2011-05-356063.CrossRefPubMedPubMedCentral

79.

Sato T, Ito T, Handa H. Cereblon-based small-molecule compounds to control neural stem cell proliferation in regenerative medicine. Front Cell Dev Biol. 2021;9: 629326. https://doi.org/10.3389/fcell.2021.629326.CrossRefPubMedPubMedCentral

80.

Kowalski TW, Gomes JDA, Garcia GBC, Fraga LR, Paixao-Cortes VR, Recamonde-Mendoza M, et al. CRL4-cereblon complex in thalidomide embryopathy: a translational investigation. Sci Rep. 2020;10(1):851. https://doi.org/10.1038/s41598-020-57512-x.CrossRefPubMedPubMedCentral

81.

Shi Q, Chen L. Cereblon: a protein crucial to the multiple functions of immunomodulatory drugs as well as cell metabolism and disease generation. J Immunol Res. 2017;2017:9130608. https://doi.org/10.1155/2017/9130608.CrossRefPubMedPubMedCentral

82.

Asatsuma-Okumura T, Ito T, Handa H. Molecular mechanisms of the teratogenic effects of thalidomide. Pharmaceuticals (Basel). 2020;13(5):95. https://doi.org/10.3390/ph13050095.CrossRef

83.

Gao S, Wang S, Fan R, Hu J. Recent advances in the molecular mechanism of thalidomide teratogenicity. Biomed Pharmacother. 2020;127: 110114. https://doi.org/10.1016/j.biopha.2020.110114.CrossRefPubMed

84.

Stewart AK. Medicine. How thalidomide works against cancer. Science. 2014;343(6168):256–7. https://doi.org/10.1126/science.1249543.CrossRefPubMedPubMedCentral

85.

Nooka AK, Lonial S. Mechanism of action and novel IMiD-based compounds and combinations in multiple myeloma. Cancer J. 2019;25(1):19–31. https://doi.org/10.1097/PPO.0000000000000354.CrossRefPubMed

86.

Krönke J, Fink EC, Hollenbach PW, MacBeth KJ, Hurst SN, Udeshi ND, et al. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature. 2015;523(7559):183–8. https://doi.org/10.1038/nature14610.CrossRefPubMedPubMedCentral

87.

Yamamoto J, Suwa T, Murase Y, Tateno S, Mizutome H, Asatsuma-Okumura T, et al. ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells. Nat Chem Biol. 2020;16(11):1208–17. https://doi.org/10.1038/s41589-020-0645-3.CrossRefPubMed

88.

Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111(6):2962–72. https://doi.org/10.1182/blood-2007-10-078022.CrossRefPubMedPubMedCentral

89.

Ribatti D. A historical perspective on milestones in multiple myeloma research. Eur J Haematol. 2018;100(3):221–8. https://doi.org/10.1111/ejh.13003.CrossRefPubMed

90.

Kyle RA. Five decades of therapy for multiple myeloma: a paradigm for therapeutic models. Leukemia. 2005;19(6):910–2. https://doi.org/10.1038/sj.leu.2403728.CrossRefPubMed

91.

McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983;2(8354):822–4. https://doi.org/10.1016/s0140-6736(83)90739-0.CrossRefPubMed

92.

Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986;67(5):1298–301.CrossRef

93.

Barlogie B, Alexanian R, Dicke KA, Zagars G, Spitzer G, Jagannath S, et al. High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood. 1987;70(3):869–72.CrossRef

94.

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;335(2):91–7. https://doi.org/10.1056/NEJM199607113350204.CrossRefPubMed

95.

Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349(26):2495–502. https://doi.org/10.1056/NEJMoa032290.CrossRefPubMed

96.

Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998;92(9):3131–6.CrossRef

97.

Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med. 1984;310(21):1353–6. https://doi.org/10.1056/NEJM198405243102104.CrossRefPubMed

98.

Barlogie B, Velasquez WS, Alexanian R, Cabanillas F. Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma. J Clin Oncol. 1989;7(10):1514–7. https://doi.org/10.1200/JCO.1989.7.10.1514.CrossRefPubMed

99.

Latif T, Chauhan N, Khan R, Moran A, Usmani SZ. Thalidomide and its analogues in the treatment of multiple myeloma. Exp Hematol Oncol. 2012;1(1):27. https://doi.org/10.1186/2162-3619-1-27.CrossRefPubMedPubMedCentral

100.

Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341(21):1565–71. https://doi.org/10.1056/NEJM199911183412102.CrossRefPubMed

101.

Hus M, Dmoszynska A, Soroka-Wojtaszko M, Jawniak D, Legiec W, Ciepnuch H, et al. Thalidomide treatment of resistant or relapsed multiple myeloma patients. Haematologica. 2001;86(4):404–8.PubMed

102.

Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood. 2001;98(2):492–4. https://doi.org/10.1182/blood.v98.2.492.CrossRefPubMed

103.

Palumbo A, Giaccone L, Bertola A, Pregno P, Bringhen S, Rus C, et al. Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica. 2001;86(4):399–403.PubMed

104.

Dimopoulos MA, Zervas K, Kouvatseas G, Galani E, Grigoraki V, Kiamouris C, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol. 2001;12(7):991–5. https://doi.org/10.1023/a:1011132808904.CrossRefPubMed

105.

Moehler TM, Neben K, Benner A, Egerer G, Krasniqi F, Ho AD, et al. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood. 2001;98(13):3846–8. https://doi.org/10.1182/blood.v98.13.3846.CrossRefPubMed

106.

Yakoub-Agha I, Attal M, Dumontet C, Delannoy V, Moreau P, Berthou C, et al. Thalidomide in patients with advanced multiple myeloma: a study of 83 patients—report of the Intergroupe Francophone du Myélome (IFM). Hematol J. 2002;3(4):185–92. https://doi.org/10.1038/sj.thj.6200175.CrossRefPubMed

107.

Tosi P, Zamagni E, Cellini C, Ronconi S, Patriarca F, Ballerini F, et al. Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma. Haematologica. 2002;87(4):408–14.PubMed

108.

Neben K, Moehler T, Benner A, Kraemer A, Egerer G, Ho AD, et al. Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma. Clin Cancer Res. 2002;8(11):3377–82.PubMed

109.

Mileshkin L, Biagi JJ, Mitchell P, Underhill C, Grigg A, Bell R, et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood. 2003;102(1):69–77. https://doi.org/10.1182/blood-2002-09-2846.CrossRefPubMed

110.

Grosbois B, Bellissant E, Moreau P, Attal M, Voillat L, Muret P, et al. Treatment of advanced multiple myeloma (MM) with thalidomide (THAL). Long term follow-up in a prospective study of 121 patients. Eur J Intern Med. 2003;4:226. https://doi.org/10.1016/S0953-6205(03)91244-1.CrossRef

111.

Kropff MH, Lang N, Bisping G, Dominé N, Innig G, Hentrich M, et al. Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br J Haematol. 2003;122(4):607–16. https://doi.org/10.1046/j.1365-2141.2003.04473.x.CrossRefPubMed

112.

Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J, et al. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol. 2003;21(14):2732–9. https://doi.org/10.1200/JCO.2003.01.055.CrossRefPubMed

113.

Waage A, Gimsing P, Juliusson G, Turesson I, Gulbrandsen N, Eriksson T, et al. Early response predicts thalidomide efficiency in patients with advanced multiple myeloma. Br J Haematol. 2004;125(2):149–55. https://doi.org/10.1111/j.1365-2141.2004.04879.x.CrossRefPubMed

114.

Richardson P, Schlossman R, Jagannath S, Alsina M, Desikan R, Blood E, et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin Proc. 2004;79(7):875–82. https://doi.org/10.4065/79.7.875.CrossRefPubMed

115.

Offidani M, Corvatta L, Marconi M, Olivieri A, Catarini M, Mele A, et al. Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma. Hematol J. 2004;5(4):312–7. https://doi.org/10.1038/sj.thj.6200401.CrossRefPubMed

116.

García-Sanz R, González-Porras JR, Hernández JM, Polo-Zarzuela M, Sureda A, Barrenetxea C, et al. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia. 2004;18(4):856–63. https://doi.org/10.1038/sj.leu.2403322.CrossRefPubMed

117.

Dimopoulos MA, Hamilos G, Zomas A, Gika D, Efstathiou E, Grigoraki V, et al. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol J. 2004;5(2):112–7. https://doi.org/10.1038/sj.thj.6200326.CrossRefPubMed

118.

Palumbo A, Bertola A, Falco P, Rosato R, Cavallo F, Giaccone L, et al. Efficacy of low-dose thalidomide and dexamethasone as first salvage regimen in multiple myeloma. Hematol J. 2004;5(4):318–24. https://doi.org/10.1038/sj.thj.6200403.CrossRefPubMed

119.

Terpos E, Mihou D, Szydlo R, Tsimirika K, Karkantaris C, Politou M, et al. The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRANKL/osteoprotegerin ratio. Leukemia. 2005;19(11):1969–76. https://doi.org/10.1038/sj.leu.2403890.CrossRefPubMed

120.

Schütt P, Ebeling P, Buttkereit U, Brandhorst D, Opalka B, Poser M, et al. Thalidomide in combination with dexamethasone for pretreated patients with multiple myeloma: serum level of soluble interleukin-2 receptor as a predictive factor for response rate and for survival. Ann Hematol. 2005;84(9):594–600. https://doi.org/10.1007/s00277-005-1007-7.CrossRefPubMed

121.

Badros AZ, Goloubeva O, Rapoport AP, Ratterree B, Gahres N, Meisenberg B, et al. Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with dexamethasone and thalidomide in relapsed multiple myeloma patients. J Clin Oncol. 2005;23(18):4089–99. https://doi.org/10.1200/JCO.2005.14.381.CrossRefPubMed

122.

Kyriakou C, Thomson K, D’Sa S, Flory A, Hanslip J, Goldstone AH, et al. Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br J Haematol. 2005;129(6):763–70. https://doi.org/10.1111/j.1365-2141.2005.05521.x.CrossRefPubMed

123.

Prince HM, Mileshkin L, Roberts A, Ganju V, Underhill C, Catalano J, et al. A multicenter phase II trial of thalidomide and celecoxib for patients with relapsed and refractory multiple myeloma. Clin Cancer Res. 2005;11(15):5504–14. https://doi.org/10.1158/1078-0432.CCR-05-0213.CrossRefPubMed

124.

Offidani M, Corvatta L, Marconi M, Visani G, Alesiani F, Brunori M, et al. Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter, phase II study. Haematologica. 2006;91(1):133–6.PubMed

125.

Hussein MA, Baz R, Srkalovic G, Agrawal N, Suppiah R, Hsi E, et al. Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma. Mayo Clin Proc. 2006;81(7):889–95. https://doi.org/10.4065/81.7.889.CrossRefPubMed

126.

Palumbo A, Avonto I, Bruno B, Falcone A, Scalzulli PR, Ambrosini MT, et al. Intermediate-dose melphalan (100 mg/m2)/bortezomib/thalidomide/dexamethasone and stem cell support in patients with refractory or relapsed myeloma. Clin Lymphoma Myeloma. 2006;6(6):475–7. https://doi.org/10.3816/CLM.2006.n.028.CrossRefPubMed

127.

Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood. 2007;109(7):2767–72. https://doi.org/10.1182/blood-2006-08-042275.CrossRefPubMed

128.

Suvannasankha A, Fausel C, Juliar BE, Yiannoutsos CT, Fisher WB, Ansari RH, et al. Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: a Hoosier Oncology Group Trial, HEM01-21. Oncologist. 2007;12(1):99–106. https://doi.org/10.1634/theoncologist.12-1-99.CrossRefPubMed

129.

Murakami H, Handa H, Abe M, et al. Low-dose thalidomide plus low-dose dexamethasone therapy in patients with refractory multiple myeloma. Eur J Haematol. 2007;79(3):234–9. https://doi.org/10.1111/j.1600-0609.2007.00908.x.CrossRefPubMed

130.

Maisnar V, Radocha J, Büchler T, Bláha V, Malý J, Hájek R. Monotherapy with low-dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment. Eur J Haematol. 2007;79(4):305–9. https://doi.org/10.1111/j.1600-0609.2007.00930.x.CrossRefPubMed

131.

Hattori Y, Okamoto S, Shimada N, Kakimoto T, Morita K, Tanigawara Y, et al. Single-institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: prognostic factors and unique toxicity profile. Cancer Sci. 2008;99(6):1243–50. https://doi.org/10.1111/j.1349-7006.2008.00792.x.CrossRefPubMed

132.

Morris TC, Kettle PJ, Drake M, Jones FC, Hull DR, Boyd K, et al. Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma. Br J Haematol. 2008;143(3):349–54. https://doi.org/10.1111/j.1365-2141.2008.07360.x.CrossRefPubMed

133.

Pineda-Roman M, Zangari M, van Rhee F, Anaissie E, Szymonifka J, Hoering A, et al. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. Leukemia. 2008;22(7):1419–27. https://doi.org/10.1038/leu.2008.99.CrossRefPubMedPubMedCentral

134.

Terpos E, Kastritis E, Roussou M, Heath D, Christoulas D, Anagnostopoulos N, et al. The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia. 2008;22(12):2247–56. https://doi.org/10.1038/leu.2008.235.CrossRefPubMed

135.

Pönisch W, Rozanski M, Goldschmidt H, Hoffmann FA, Boldt T, Schwarzer A, et al. Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial. Br J Haematol. 2008;143(2):191–200. https://doi.org/10.1111/j.1365-2141.2008.07076.x.CrossRefPubMed

136.

Srikanth M, Davies FE, Wu P, Jenner MW, Ethell ME, Potter MN, et al. Survival and outcome of blastoid variant myeloma following treatment with the novel thalidomide containing regime DT-PACE. Eur J Haematol. 2008;81(6):432–6. https://doi.org/10.1111/j.1600-0609.2008.01131.x.CrossRefPubMed

137.

Kim YK, Sohn SK, Lee JH, Yang DH, Moon JH, Ahn JS, et al. Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study. Ann Hematol. 2010;89(5):475–82. https://doi.org/10.1007/s00277-009-0856-x.CrossRefPubMed

138.

Palumbo A, Larocca A, Falco P, Sanpaolo G, Falcone AP, Federico V, et al. Lenalidomide, melphalan, prednisone and thalidomide (RMPT) for relapsed/refractory multiple myeloma. Leukemia. 2010;24(5):1037–42. https://doi.org/10.1038/leu.2010.58.CrossRefPubMed

139.

Lee SS, Suh C, Kim BS, Chung J, Joo YD, Ryoo HM, et al. Bortezomib, doxorubicin, and dexamethasone combination therapy followed by thalidomide and dexamethasone consolidation as a salvage treatment for relapsed or refractory multiple myeloma: analysis of efficacy and safety. Ann Hematol. 2010;89(9):905–12. https://doi.org/10.1007/s00277-010-0943-z.CrossRefPubMed

140.

Hus M, Grzasko N, Szostek M, Pluta A, Helbig G, Woszczyk D, et al. Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma. Ann Hematol. 2011;90(10):1161–6. https://doi.org/10.1007/s00277-011-1276-2.CrossRefPubMedPubMedCentral

141.

Offidani M, Corvatta L, Polloni C, Gentili S, Mele A, Rizzi R, et al. Thalidomide, dexamethasone, Doxil and Velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed-refractory multiple myeloma. Ann Hematol. 2011;90(12):1449–56. https://doi.org/10.1007/s00277-011-1217-0.CrossRefPubMed

142.

Zamagni E, Petrucci A, Tosi P, Tacchetti P, Perrone G, Brioli A, et al. Long-term results of thalidomide and dexamethasone (thal-dex) as therapy of first relapse in multiple myeloma. Ann Hematol. 2012;91(3):419–26. https://doi.org/10.1007/s00277-011-1320-2.CrossRefPubMed

143.

Yakoub-Agha I, Mary JY, Hulin C, Doyen C, Marit G, Benboubker L, et al. Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome. Eur J Haematol. 2012;88(3):249–59. https://doi.org/10.1111/j.1600-0609.2011.01729.x.CrossRefPubMed

144.

Kropff M, Baylon HG, Hillengass J, Robak T, Hajek R, Liebisch P, et al. Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica. 2012;97(5):784–91. https://doi.org/10.3324/haematol.2011.044271.CrossRefPubMedPubMedCentral

145.

Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, et al. Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012;88(6):485–96. https://doi.org/10.1111/j.1600-0609.2012.01775.x.CrossRefPubMedPubMedCentral

146.

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;30(20):2475–82. https://doi.org/10.1200/JCO.2011.37.4918.CrossRefPubMed

147.

Offidani M, Polloni C, Cavallo F, Liberati AM, Ballanti S, Pulini S, et al. Phase II study of melphalan, thalidomide and prednisone combined with oral panobinostat in patients with relapsed/refractory multiple myeloma. Leuk Lymphoma. 2012;53(9):1722–7. https://doi.org/10.3109/10428194.2012.664844.CrossRefPubMed

148.

Geng C, Hou J, Zhao Y, Ke X, Wang Z, Qiu L, et al. A multicenter, open-label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma. Am J Hematol. 2014;89(11):1037–42. https://doi.org/10.1002/ajh.23822.CrossRefPubMed

149.

Schey S, Brown SR, Tillotson AL, Yong K, Williams C, Davies F, et al. 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):336–48. https://doi.org/10.1111/bjh.13435.CrossRefPubMed

150.

Mateos MV, Granell M, Oriol A, Martinez-Lopez J, Blade J, Hernandez MT, et al. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma. Br J Haematol. 2016;175(3):448–56. https://doi.org/10.1111/bjh.14263.CrossRefPubMed

151.

Popat R, Brown SR, Flanagan L, Hall A, Gregory W, Kishore B, et al. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016;3(12):e572–80. https://doi.org/10.1016/S2352-3026(16)30165-X.CrossRefPubMed

152.

Kwon J, Min CK, Kim K, Han JJ, Moon JH, Kang HJ, et al. Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study. Cancer Med. 2017;6(1):100–8. https://doi.org/10.1002/cam4.970.CrossRefPubMed

153.

Leng Y, Hou J, Jin J, Zhang M, Ke X, Jiang B, et al. Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study. Cancer Chemother Pharmacol. 2017;79(6):1141–9. https://doi.org/10.1007/s00280-017-3310-0.CrossRefPubMed

154.

Mian M, Pescosta N, Badiali S, Cappelletto PC, Marcheselli L, Luminari S, et al. Phase II trial to investigate efficacy and safety of bendamustine, dexamethasone and thalidomide in relapsed or refractory multiple myeloma patients after treatment with lenalidomide and bortezomib. Br J Haematol. 2019;185(5):944–7. https://doi.org/10.1111/bjh.15645.CrossRefPubMed

155.

Ludwig H, Poenisch W, Knop S, Egle A, Schreder M, Lechner D, et al. Ixazomib–thalidomide–dexamethasone for induction therapy followed by ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. Br J Cancer. 2019;121(9):751–7. https://doi.org/10.1038/s41416-019-0581-8.CrossRefPubMedPubMedCentral

156.

Lee HC, Shah JJ, Feng L, Morphey A, Johnson RJ, Wesson ET, et al. A phase I/II trial of the combination of lenalidomide, thalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Am J Hematol. 2019;94(12):E319–22. https://doi.org/10.1002/ajh.25633.CrossRefPubMed

157.

Bergin K, Yuen F, Wallington-Beddoe C, Kalff A, Sirdesai S, Reynolds J, et al. A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16–02 trial. Br J Haematol. 2021;194(3):580–6. https://doi.org/10.1111/bjh.17504.CrossRefPubMed

158.

Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691–5. https://doi.org/10.1182/blood-2010-10-299487.CrossRefPubMedPubMedCentral

159.

Glasmacher A, Hahn C, Hoffmann F, Naumann R, Goldschmidt H, von Lilienfeld-Toal M, et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol. 2006;132(5):584–93. https://doi.org/10.1111/j.1365-2141.2005.05914.x.CrossRefPubMed

160.

Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood. 2000;96(9):2943–50.CrossRef

161.

von Lilienfeld-Toal M, Hahn-Ast C, Furkert K, Hoffmann F, Naumann R, Bargou R, et al. A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur J Haematol. 2008;81(4):247–52. https://doi.org/10.1111/j.1600-0609.2008.01121.x.CrossRef

162.

Lee JH, Kim SH. Treatment of relapsed and refractory multiple myeloma. Blood Res. 2020;55(S1):S43–53. https://doi.org/10.5045/br.2020.S008.CrossRefPubMed

163.

Bogeljić Patekar M, Milunović V, Mišura Jakobac K, Perica D, Mandac Rogulj I, Kursar M, et al. Bendamustine: an old drug in the new era for patients with non-Hodgkin lymphomas and chronic lymphocytic leukemia. Acta Clin Croat. 2018;57(3):542–53. https://doi.org/10.20471/acc.2018.57.03.18.CrossRefPubMedPubMedCentral

164.

Kumar SK, Krishnan A, LaPlant B, Laumann K, Roy V, Zimmerman T, et al. Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma. Am J Hematol. 2015;90(12):1106–10. https://doi.org/10.1002/ajh.24181.CrossRefPubMed

165.

Mey UJ, Brugger W, Schwarb H, Pederiva S, Schwarzer A, Dechow T, et al. Bendamustine, lenalidomide and dexamethasone (BRd) has high activity as 2nd -line therapy for relapsed and refractory multiple myeloma—a phase II trial. Br J Haematol. 2017;176(5):770–82. https://doi.org/10.1111/bjh.14481.CrossRefPubMed

166.

Dhakal B, D’Souza A, Hamadani M, Arce-Lara C, Schroeder K, Chhabra S, et al. Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma. Blood Cancer J. 2019;9(8):56. https://doi.org/10.1038/s41408-019-0219-3.CrossRefPubMedPubMedCentral

167.

Zangari M, Anaissie E, Barlogie B, Badros A, Desikan R, Gopal AV, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood. 2001;98(5):1614–5. https://doi.org/10.1182/blood.v98.5.1614.CrossRefPubMed

168.

Gerrie AS, Mikhael JR, Cheng L, Jiang H, Kukreti V, Panzarella T, et al. D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma. Br J Haematol. 2013;161(6):802–10. https://doi.org/10.1111/bjh.12325.CrossRefPubMed

169.

Buda G, Orciuolo E, Galimberti S, Ghio F, Petrini M. VDTPACE as salvage therapy for heavily pretreated MM patients. Blood. 2013;122(21):5377. https://doi.org/10.1182/blood.V122.21.5377.5377.CrossRef

170.

Beyer K, Rosner S, Woo KM, Devlin SM, Landau H, Hassoun H, et al. Analysis of VDT-PACE utilization in multiple myeloma patients treated at MSKCC for relapsed disease or cytoreduction and stem cell mobilization after initial induction therapy. Blood. 2014;124(21):3459. https://doi.org/10.1182/blood.V124.21.3459.3459.CrossRef

171.

Ainley L, Chavda SJ, Counsell N, Cheesman S, Newrick F, Horder J, et al. DT-PACE/ESHAP chemotherapy regimens as salvage therapy for multiple myeloma prior to autologous stem cell transplantation. Br J Haematol. 2021;192(3):e73–7. https://doi.org/10.1111/bjh.17248.CrossRefPubMed

172.

Lakshman A, Singh PP, Rajkumar SV, Dispenzieri A, Lacy MQ, Gertz MA, et al. Efficacy of VDT PACE-like regimens in treatment of relapsed/refractory multiple myeloma. Am J Hematol. 2018;93(2):179–86. https://doi.org/10.1002/ajh.24954.CrossRefPubMed

173.

Pineda-Roman M, Zangari M, Haessler J, Anaissie E, Tricot G, van Rhee F, et al. Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Br J Haematol. 2008;140(6):625–34. https://doi.org/10.1111/j.1365-2141.2007.06921.x.CrossRefPubMedPubMedCentral

174.

Koeppen S. Treatment of multiple myeloma: thalidomide-, bortezomib-, and lenalidomide-induced peripheral neuropathy. Oncol Res Treat. 2014;37(9):506–13. https://doi.org/10.1159/000365534.CrossRefPubMed

175.

Mohan M, Matin A, Davies FE. Update on the optimal use of bortezomib in the treatment of multiple myeloma. Cancer Manag Res. 2017;9:51–63. https://doi.org/10.2147/CMAR.S105163.CrossRefPubMedPubMedCentral

176.

Mikhael JR, Reeder CB, Libby EN, Costa LJ, Bergsagel PL, Buadi F, et al. Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma. Br J Haematol. 2015;169(2):219–27. https://doi.org/10.1111/bjh.13296.CrossRefPubMedPubMedCentral

177.

Waxman AJ, Clasen S, Hwang WT, Garfall A, Vogl DT, Carver J, et al. Carfilzomib-associated cardiovascular adverse events: a systematic review and meta-analysis. JAMA Oncol. 2018;4(3): e174519. https://doi.org/10.1001/jamaoncol.2017.4519.CrossRefPubMed

178.

Chng W, Lin C, Li X, Nagarajan C, Yoon S, Durie BGM. Phase 2 study of daratumumab in combination with thalidomide and dexamethasone in Asian patients with relapsed/refractory myeloma (RRMM)—interim analysis of a trial by the Asian Myeloma Network (AMN). Blood. 2020;136(Suppl 1):21. https://doi.org/10.1182/blood-2020-139092.CrossRef

179.

Chanan-Khan A. Immunomodulating drugs for the treatment of cancer. 1st ed. Philadelphia: Lippincott Williams & Wilkins: Wolters Kluwer; 2011.

180.

Sonneveld P, De Wit E, Moreau P. How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients? Crit Rev Oncol Hematol. 2017;112:153–70. https://doi.org/10.1016/j.critrevonc.2017.02.007.CrossRefPubMed

181.

Thompson JL, Hansen LA. Thalidomide dosing in patients with relapsed or refractory multiple myeloma. Ann Pharmacother. 2003;37(4):571–6. https://doi.org/10.1345/aph.1A155.CrossRefPubMed

182.

Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23. https://doi.org/10.1038/sj.leu.2405062.CrossRefPubMed

183.

Guglielmelli T, Petrucci MT, Saglio G, Palumbo A. Thalidomide after lenalidomide: a possible treatment regimen in relapsed refractory multiple myeloma patients. Br J Haematol. 2011;152(1):108–10. https://doi.org/10.1111/j.1365-2141.2010.08416.x.CrossRefPubMed

184.

Dingli D, Ailawadhi S, Bergsagel PL, Buadi FK, Dispenzieri A, Fonseca R, et al. Therapy for relapsed multiple myeloma: guidelines from the mayo stratification for myeloma and risk-adapted therapy. Mayo Clin Proc. 2017;92(4):578–98. https://doi.org/10.1016/j.mayocp.2017.01.003.CrossRefPubMed

185.

Palumbo A, Cerrato C. Diagnosis and therapy of multiple myeloma. Korean J Intern Med. 2013;28(3):263–73. https://doi.org/10.3904/kjim.2013.28.3.263.CrossRefPubMedPubMedCentral

186.

Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR. Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006;24(3):431–6. https://doi.org/10.1200/JCO.2005.03.0221.CrossRefPubMed

187.

Paul B, Lipe B, Ocio EM, Usmani SZ. Induction therapy for newly diagnosed multiple myeloma. Am Soc Clin Oncol Educ Book. 2019;39:e176–86. https://doi.org/10.1200/EDBK_238527.CrossRefPubMed

188.

Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, Blau IW, et al. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia. 2015;29(8):1721–9. https://doi.org/10.1038/leu.2015.80.CrossRefPubMed

189.

Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016;127(21):2569–74. https://doi.org/10.1182/blood-2016-01-693580.CrossRefPubMed

190.

Leiba M, Kedmi M, Duek A, Freidman T, Weiss M, Leiba R, et al. Bortezomib-cyclophosphamide-dexamethasone (VCD) versus bortezomib-thalidomide-dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br J Haematol. 2014;166(5):702–10. https://doi.org/10.1111/bjh.12946.CrossRefPubMed

191.

Rosinol L, Hebraud B, Oriol A, Colin AL, Tamayo RR, Hulin C, et al. Integrated analysis of bortezomib–lenalidomide–dexamethasone vs bortezomib–thalidomide–dexamethasone in transplant-eligible newly diagnosed myeloma. Clin Lymphoma Myeloma Leuk. 2019;19(Suppl 10):1–2.

192.

Zangari M, van Rhee F, Anaissie E, Pineda-Roman M, Haessler J, Crowley J, et al. Eight-year median survival in multiple myeloma after total therapy 2: roles of thalidomide and consolidation chemotherapy in the context of total therapy 1. Br J Haematol. 2008;141(4):433–44. https://doi.org/10.1111/j.1365-2141.2008.06982.x.CrossRefPubMedPubMedCentral

193.

Wester R, van der Holt B, Asselbergs E, Zweegman S, Kersten MJ, Vellenga E, et al. Phase II study of carfilzomib, thalidomide, and low-dose dexamethasone as induction and consolidation in newly diagnosed, transplant eligible patients with multiple myeloma; the Carthadex trial. Haematologica. 2019;104(11):2265–73. https://doi.org/10.3324/haematol.2018.205476.CrossRefPubMedPubMedCentral

194.

Paumgartten FJR. The tale of lenalidomide clinical superiority over thalidomide and regulatory and cost-effectiveness issues. Cien Saude Colet. 2019;24(10):3783–92. https://doi.org/10.1590/1413-812320182410.28522017.CrossRefPubMed

195.

Lee HS, Min CK, Lee JJ, Kim K, Kim SJ, Yoon DH, et al. The clinical impact of thalidomide maintenance after autologous stem cell transplantation in patients with newly diagnosed multiple myeloma in real clinical practice of Korea. Ann Hematol. 2016;95(6):911–9. https://doi.org/10.1007/s00277-016-2660-8.CrossRefPubMed

196.

Ludwig H, Durie BG, McCarthy P, Palumbo A, San Miguel J, Barlogie B, et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood. 2012;119(13):3003–15. https://doi.org/10.1182/blood-2011-11-374249.CrossRefPubMedPubMedCentral

197.

Berenson JR. Antitumor effects of bisphosphonates: from the laboratory to the clinic. Curr Opin Support Palliat Care. 2011;5(3):233–40. https://doi.org/10.1097/SPC.0b013e328349dc17.CrossRefPubMed

198.

Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108(10):3289–94. https://doi.org/10.1182/blood-2006-05-022962.CrossRefPubMed

199.

Dimopoulos MA, Jakubowiak AJ, McCarthy PL, Orlowski RZ, Attal M, Bladé J, et al. Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma. Blood Cancer J. 2020;10(2):17. https://doi.org/10.1038/s41408-020-0273-x.CrossRefPubMedPubMedCentral

200.

Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012;119(1):7–15. https://doi.org/10.1182/blood-2011-06-357038.CrossRefPubMed

201.

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;28(7):1209–14. https://doi.org/10.1200/JCO.2009.25.6081.CrossRefPubMedPubMedCentral

202.

Ramasamy K, Dhanasiri S, Thom H, Buchanan V, Robinson S, D’Souza VK, et al. Relative efficacy of treatment options in transplant-ineligible newly diagnosed multiple myeloma: results from a systematic literature review and network meta-analysis. Leuk Lymphoma. 2020;61(3):668–79. https://doi.org/10.1080/10428194.2019.1683736.CrossRefPubMed

203.

Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksaç M, 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;118(5):1239–47. https://doi.org/10.1182/blood-2011-03-341669.CrossRefPubMed

204.

Kaweme NM, Changwe GJ, Zhou F. Approaches and challenges in the management of multiple myeloma in the very old: future treatment prospects. Front Med (Lausanne). 2021;8: 612696. https://doi.org/10.3389/fmed.2021.612696.CrossRefPubMedPubMedCentral

205.

Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906–17. https://doi.org/10.1056/NEJMoa1402551.CrossRefPubMed

206.

Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, et al. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015;126(11):1294–301. https://doi.org/10.1182/blood-2014-12-613927.CrossRefPubMedPubMedCentral

207.

Zweegman S, van der Holt B, Mellqvist UH, Salomo M, Bos GM, Levin MD, et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016;127(9):1109–16. https://doi.org/10.1182/blood-2015-11-679415.CrossRefPubMed

208.

Gavriatopoulou M, Terpos E, Kastritis E, Dimopoulos MA. Current treatments for renal failure due to multiple myeloma. Expert Opin Pharmacother. 2016;17(16):2165–77. https://doi.org/10.1080/14656566.2016.1236915.CrossRefPubMed

209.

Chu P. Managing multiple myeloma patients with renal failure. Hong Kong J Nephrol. 2013;15(2):62–7. https://doi.org/10.1016/j.hkjn.2013.09.001.CrossRef

210.

Bozic B, Rutner J, Zheng C, Ruckser R, Selimi F, Racz K, et al. Advances in the treatment of relapsed and refractory multiple myeloma in patients with renal insufficiency: novel agents, immunotherapies and beyond. Cancers (Basel). 2021;13(20):5036. https://doi.org/10.3390/cancers13205036.CrossRefPubMedPubMedCentral

211.

Bridoux F, Leung N, Belmouaz M, Royal V, Ronco P, Nasr SH, et al. Management of acute kidney injury in symptomatic multiple myeloma. Kidney Int. 2021;99(3):570–80. https://doi.org/10.1016/j.kint.2020.11.010.CrossRefPubMed

212.

Gavriatopoulou M, Terpos E, Dimopoulos MA. IMiDs for myeloma induced renal impairment. Oncotarget. 2018;9(84):35476–7. https://doi.org/10.18632/oncotarget.26270.CrossRefPubMedPubMedCentral

213.

Wanchoo R, Abudayyeh A, Doshi M, Edeani A, Glezerman IG, Monga D, et al. Renal toxicities of novel agents used for treatment of multiple myeloma. Clin J Am Soc Nephrol. 2017;12(1):176–89. https://doi.org/10.2215/CJN.06100616.CrossRefPubMed

214.

Palumbo A, Facon T, Sonneveld P, Bladè J, Offidani M, Gay F, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood. 2008;111(8):3968–77. https://doi.org/10.1182/blood-2007-10-117457.CrossRefPubMed

215.

Chen N, Lau H, Kong L, Kumar G, Zeldis JB, Knight R, et al. Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol. 2007;47(12):1466–75. https://doi.org/10.1177/0091270007309563.CrossRefPubMed

216.

Tosi P, Zamagni E, Cellini C, Cangini D, Tacchetti P, Tura S, et al. Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure. Eur J Haematol. 2004;73(2):98–103. https://doi.org/10.1111/j.1600-0609.2004.00272.x.CrossRefPubMed

217.

Kastritis E, Anagnostopoulos A, Roussou M, Gika D, Matsouka C, Barmparousi D, et al. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents. Haematologica. 2007;92(4):546–9. https://doi.org/10.3324/haematol.10759.CrossRefPubMed

218.

Tosi P, Zamagni E, Tacchetti P, Ceccolini M, Perrone G, Brioli A, et al. Thalidomide-dexamethasone as induction therapy before autologous stem cell transplantation in patients with newly diagnosed multiple myeloma and renal insufficiency. Biol Blood Marrow Transplant. 2010;16(8):1115–21. https://doi.org/10.1016/j.bbmt.2010.02.020.CrossRefPubMed

219.

Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, et al. Safety and efficacy of bortezomib–melphalan–prednisone–thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib–melphalan–prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011;118(22):5759–66. https://doi.org/10.1182/blood-2011-05-353995.CrossRefPubMed

220.

Ramasamy K, Hazel B, Mahmood S, Corderoy S, Schey S. Bendamustine in combination with thalidomide and dexamethasone is an effective therapy for myeloma patients with end stage renal disease. Br J Haematol. 2011;155(5):632–4. https://doi.org/10.1111/j.1365-2141.2011.08754.x.CrossRefPubMed

221.

Dimopoulos MA, Roussou M, Gkotzamanidou M, Nikitas N, Psimenou E, Mparmparoussi D, et al. The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia. 2013;27(2):423–9. https://doi.org/10.1038/leu.2012.182.CrossRefPubMed

222.

Dimopoulos MA, Cheung MC, Roussel M. Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma. Haematologica. 2016;101(3):363–70. https://doi.org/10.3324/haematol.2015.133629.CrossRefPubMedPubMedCentral

223.

Ramasamy K, Drayson MT, Iqbal G, Stalker V, Akhtar S, Dunn J, et al. Optimal—a study of bortezomib, bendamustine and dexamethasone (BBD) vs thalidomide, bendamustine and dexamethasone (BTD) in patients with renal failure defined as an Egfr below 30 Mls/Min. Blood. 2019;134(Suppl 1):3135. https://doi.org/10.1182/blood-2019-128157.CrossRef

224.

Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119(19):4375–82. https://doi.org/10.1182/blood-2011-11-395749.CrossRefPubMed

225.

Schmitt S, Mailaender V, Egerer G, Leo A, Becker S, Reinhardt P, et al. Successful autologous peripheral blood stem cell transplantation in a Jehovah’s Witness with multiple myeloma: review of literature and recommendations for high-dose chemotherapy without support of allogeneic blood products. Int J Hematol. 2008;87(3):289–97. https://doi.org/10.1007/s12185-008-0055-x.CrossRefPubMed

226.

Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319–31. https://doi.org/10.1056/NEJMoa1607751.CrossRefPubMed

227.

Xia R, Cheng Y, Han X, Wei Y, Wei X. Ikaros proteins in tumor: current perspectives and new developments. Front Mol Biosci. 2021;8: 788440. https://doi.org/10.3389/fmolb.2021.788440.CrossRefPubMedPubMedCentral

228.

Swan D, Routledge D, Harrison S. The evolving status of immunotherapies in multiple myeloma: the future role of bispecific antibodies. Br J Haematol. 2022;196(3):488–506. https://doi.org/10.1111/bjh.17805.CrossRefPubMed

229.

Hernández-Rivas JÁ, Ríos-Tamayo R, Encinas C, Alonso R, Lahuerta JJ. The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies. Biomark Res. 2022;10(1):1. https://doi.org/10.1186/s40364-021-00344-2.CrossRefPubMedPubMedCentral

230.

Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314–24. https://doi.org/10.1016/S0140-6736(21)00933-8.CrossRefPubMed

231.

Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2022;33(3):259–75. https://doi.org/10.1016/j.annonc.2021.12.003.CrossRefPubMed

232.

Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari 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):207–21. https://doi.org/10.1016/S1470-2045(19)30788-0.CrossRefPubMed

233.

Becnel MR, Lee HC. The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma. Ther Adv Hematol. 2020;11:2040620720979813. https://doi.org/10.1177/2040620720979813.CrossRefPubMedPubMedCentral

234.

Popat R, Nooka A, Stockerl-Goldstein K, Abonour R, Ramaekers R, Khot A, et al. DREAMM-6: safety, tolerability and clinical activity of belantamab mafodotin (Belamaf) in combination with bortezomib/dexamethasone (BorDex) in relapsed/refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl 1):19–20. https://doi.org/10.1182/blood-2020-139332.CrossRef

235.

Reece D, Kouroukis CT, Leblanc R, Sebag M, Song K, Ashkenas J. Practical approaches to the use of lenalidomide in multiple myeloma: a Canadian consensus. Adv Hematol. 2012;2012: 621958. https://doi.org/10.1155/2012/621958.CrossRefPubMedPubMedCentral

236.

Works M, Soni N, Hauskins C, Sierra C, Baturevych A, Jones JC, et al. Anti-B-cell maturation antigen chimeric antigen receptor T cell function against multiple myeloma is enhanced in the presence of lenalidomide. Mol Cancer Ther. 2019;18(12):2246–57. https://doi.org/10.1158/1535-7163.MCT-18-1146.CrossRefPubMed

237.

Wang X, Walter M, Urak R, Weng L, Huynh C, Lim L, et al. Lenalidomide enhances the function of CS1 chimeric antigen receptor-redirected T cells against multiple myeloma. Clin Cancer Res. 2018;24(1):106–19. https://doi.org/10.1158/1078-0432.CCR-17-0344.CrossRefPubMed

238.

Teoh PJ, Chng WJ. CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer J. 2021;11(4):84. https://doi.org/10.1038/s41408-021-00469-5.CrossRefPubMedPubMedCentral

239.

Cho SF, Lin L, Xing L, Li Y, Wen K, Yu T, et al. The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models. Blood Adv. 2020;4(17):4195–207. https://doi.org/10.1182/bloodadvances.2020002524.CrossRefPubMedPubMedCentral

240.

Louvet C, Nadeem O, Smith EL. Finding the optimal partner to pair with bispecific antibody therapy for multiple myeloma. Blood Cancer Discov. 2021;2(4):297–9. https://doi.org/10.1158/2643-3230.BCD-21-0073.CrossRefPubMedPubMedCentral

241.

Jan M, Scarfò I, Larson RC, Walker A, Schmidts A, Guirguis AA, et al. Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide. Sci Transl Med. 2021;13(575):eabb6295. https://doi.org/10.1126/scitranslmed.abb6295.CrossRefPubMedPubMedCentral

242.

Bhattacharya K, Bentley JP, Ramachandran S, Chang Y, Banahan BF 3rd, Shah R, et al. Phase-specific and lifetime costs of multiple myeloma among older adults in the US. JAMA Netw Open. 2021;4(7): e2116357. https://doi.org/10.1001/jamanetworkopen.2021.16357.CrossRefPubMedPubMedCentral

243.

Blommestein HM, Franken MG, van Beurden-Tan CHY, Blijlevens NMA, Huijgens PC, Sonneveld P, et al. Cost-effectiveness of novel treatment sequences for transplant-ineligible patients with multiple myeloma. JAMA Netw Open. 2021;4(3): e213497. https://doi.org/10.1001/jamanetworkopen.2021.3497.CrossRefPubMedPubMedCentral

Titel: What’s Old is New: The Past, Present and Future Role of Thalidomide in the Modern-Day Management of Multiple Myeloma
verfasst von: Bruno Almeida Costa
Tarek H. Mouhieddine
Joshua Richter
Publikationsdatum: 30.06.2022
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 4/2022
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-022-00897-8

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

What’s Old is New: The Past, Present and Future Role of Thalidomide in the Modern-Day Management of Multiple Myeloma

Abstract

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2022

Pattern of Clinical Progression Until Metastatic Castration-Resistant Prostate Cancer: An Epidemiological Study from the European Prostate Cancer Registry

Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer

Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP

Efficacy and Safety of Immunotherapy-Based Combinations as First-Line Therapy for Metastatic Renal Cell Carcinoma in Patients Who Do Not Meet Trial Eligibility Criteria

Comment on: “Thromboembolism in Patients with Metastatic Renal Cell Carcinoma Treated with Immunotherapy”

Real-World Treatment with Nivolumab or Cabozantinib for Metastatic Renal Cell Carcinoma (mRCC) in the Veneto Region of Italy: Results of AMOUR Study

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Onkologie