Current therapeutic uses of lenalidomide in multiple myeloma

Expert Opinion on Investigational Drugs

Volumn 15, Issue 2, 2006, Pages 171-179

  Hideshima, Teru ^a   Richardson, Paul G ^a   Anderson, Kenneth C ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Clinical trial; Immunomodulatory drug; Lenalidomide; Multiple myeloma; Thalidomide

Indexed keywords

3 (4 AMINO 1,3 DIHYDRO 1,3 DIOXO 2H ISOINDOL 2 YL)GLUTARIMIDE; ACETYLSALICYLIC ACID; ALKYLATING AGENT; ANTHRACYCLINE DERIVATIVE; BASIC FIBROBLAST GROWTH FACTOR; BISPHOSPHONIC ACID DERIVATIVE; BORTEZOMIB; CORTICOSTEROID; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN DEPENDENT KINASE INHIBITOR 1B; CYCLOOXYGENASE 2; DEXAMETHASONE; FIBRONECTIN; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; LENALIDOMIDE; PROSTAGLANDIN E2; PROTEIN KINASE B; RAPAMYCIN; RECOMBINANT GROWTH FACTOR; SOMATOMEDIN C; STROMAL CELL DERIVED FACTOR 1ALPHA; THALIDOMIDE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VASCULOTROPIN;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOLOGOUS BONE MARROW TRANSPLANTATION; BLOOD TOXICITY; BONE MARROW; BONE MARROW SUPPRESSION; BONE METASTASIS; CANCER ADJUVANT THERAPY; CANCER INHIBITION; CANCER RELAPSE; CANCER RESISTANCE; CARCINOGENESIS; CELL ADHESION; CLINICAL TRIAL; CONSTIPATION; CYTOKINE RELEASE; DEEP VEIN THROMBOSIS; DOSE RESPONSE; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG ACTIVATION; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG POTENCY; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; FATIGUE; FEBRILE NEUTROPENIA; GRAFT VERSUS HOST REACTION; HEART ATRIUM FIBRILLATION; HUMAN; IMMUNOMODULATION; KIDNEY DISEASE; LIVER DISEASE; LUNG EMBOLISM; MAXIMUM TOLERATED DOSE; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; NEUROTOXICITY; NEUTROPENIA; NONHUMAN; PERIPHERAL NEUROPATHY; QUALITY OF LIFE; SEDATION; SIDE EFFECT; SIGNAL TRANSDUCTION; SOMNOLENCE; STRUCTURE ACTIVITY RELATION; TERATOGENICITY; THROMBOCYTOPENIA; TREMOR; TUMOR IMMUNITY;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; MULTIPLE MYELOMA; THALIDOMIDE;

EID: 32844472513     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.15.2.171     Document Type: Article

References (81)

1. KUEHL WM, BERGSAGEL PL: Multiple myeloma: evolving genetic events and host interactions. Nat. Rev. Cancer (2002) 2:175-187.
2. HIDESHIMA T, ANDERSON KC: Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat. Rev. Cancer (2002) 2:927-937.
3. HIDESHIMA T, RICHARDSON P, ANDERSON KC: Novel therapeutic approaches for multiple myeloma. Immunol. Rev. (2003) 194:164-176.
4. TEOH G, ANDERSON KC: Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma. Hematol. Oncol. Clin. North Am. (1997) 11:27-42.
5. DAMIANO JS, CRESS AE, HAZLEHURST LA, SHTIL AA, DALTON WS: Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood (1999) 93:1658-1667.
6. DAMIANO JS, DALTON WS: Integrin-mediated drug resistance in multiple myeloma. Leuk. Lymphoma (2000) 38:71-81.
7. HAZLEHURST LA, DAMIANO JS, BUYUKSAL I, PLEDGER WJ, DALTON WS: Adhesion to fibronectin via β1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene (2000) 19:4319-4327.
8. UCHIYAMA H, BARUT BA, MOHRBACHER AF, CHAUHAN D, ANDERSON KC: Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates IL-6 secretion. Blood (1993) 82:3712-3720.
9. CHAUHAN D, UCHIYAMA H, AKBARALI Y et al.: Myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-κB. Blood (1996) 87:1104-1112.
10. HIDESHIMA T, CHAUHAN D, RICHARDSON P et al.: NF-κB as a therapeutic target in multiple myeloma. J. Biol. Chem. (2002) 277:16639-16647.
11. HIDESHIMA T, CHAUHAN D, SCHLOSSMAN RL, RICHARDSON PR, ANDERSON KC: Role of TNF-α in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene (2001) 20:4519-4527.
12. URASHIMA M, OGATA A, CHAUHAN D et al.: Transforming growth factor β1: differential effects on multiple myeloma versus normal B cells. Blood (1996) 87:1928-1938.
13. HAYASHI T, HIDESHIMA T, NGUYEN AN et al.: TGF-β receptor I kinase inhibitor downregulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment. Clin. Cancer Res. (2004) 10:7540-7546.
14. DANKBAR B, PADRO T, LEO R et al.: Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood (2000) 95:2630-2636.
15. FREUND GG, KULAS DT, MOONEY RA: Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226. J. Immunol. (1993) 151:1811.
16. NISHIMOTO N, OGATA A, SHIMA Y et al.: Leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130. J. Exp. Med. (1994) 179:1343-1347.
17. BORSET M, WAAGE A, BREKKE OL, HELSETH E: TNF and IL-6 are potent growth factors for OH-2, a novel human myeloma cell line. Eur. J. Haematol. (1994) 53:31.
18. LICHTENSTEIN A, TU Y, FADY C, VESCIO R, BERENSON J: Interleukin-6 inhibits apoptosis of malignant plasma cells. Cell Immunol. (1995) 162:248-255.
19. CHAUHAN D, KHARBANDA S, OGATA A et al.: Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood (1997) 89:227-234.
20. OGATA A, CHAUHAN D, TEOH G et al.: Interleukin-6 triggers cell growth via the ras-dependent mitogen-activated protein kinase cascade. J. Immunol. (1997) 159:2212-2221.
21. OGATA A, CHAUHAN D, URASHIMA M, TEOH G, TREON SP, ANDERSON KC: Blockade of mitogen-activated protein kinase cascade signaling in interleukin-6 independent multiple myeloma cells. Clin. Cancer Res. (1997) 3:1017-1022.
22. VANDERKERKEN K, ASOSINGH K, BRAET F, VAN RIET I, VAN CAMP B: Insulin-like growth factor-1 acts as a chemoattractant factor for 5T2 multiple myeloma cells. Blood (1999) 93:235-241.
23. PUTHIER D, BATAILLE R, AMIOT M: IL-6 up-regulates mcl-1 in human myeloma cells through JAK/STAT rather than ras/MAP kinase pathway. Eur. J. Immunol. (1999) 29:3945-3950.
24. CHAUHAN D, PANDEY PT, TREON S et al.: SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apopotosis in multiple myeloma cells. J. Biol. Chem. (2000) 275:27845-27850.
25. HIDESHIMA T, NAKAMURA N, CHAUHAN D, ANDERSON KC: Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene (2001) 20:5991-6000.
26. PODAR K, TAI YT, DAVIES FE et al.: Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood (2001) 98:428-435.
27. PODAR K, TAI YT, LIN BK et al.: Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with β1 integrin- and phosphatidylinositol 3-kinase-dependent PKC-α activation. J. Biol. Chem. (2002) 277:7875-7881.
28. HIDESHIMA T, CHAUHAN D, HAYASHI T et al.: The biological sequelae of stromal cell-derived factor-1α in multiple myeloma. Mol. Cancer Ther. (2002) 1:539-544.
29. MITSIADES CS, MITSIADES N, POULAKI V et al.: Activation of NF-κB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications. Oncogene (2002) 21:5673-5683.
30. MITSIADES CS, MITSIADES NS, McMULLAN CJ et al.: Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell (2004) 5:221-230.
31. GREGORY WM, RICHARDS MA, MALPAS JS: Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J. Clin. Oncol. (1992) 10:334-342.
32. GROUP MT: 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) 16:3832-3842.
33. FERMAND JP, RAVAUD P, CHEVRET S 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) 92:3131-3136.
34. LENHOFF S, HJORTH M, HOLMBERG EI et al.: Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Blood (2000) 95:7-11.
35. DESIKAN R, BARLOGIE B, SAWYER J et al.: Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood (2000) 95:4008-4010.
36. ATTAL M, HAROUSSEAU JL, FACON T et al.: Single versus double autologous stem-cell transplantation for multiple myeloma. N. Engl. J. Med. (2003) 349:2495-2502.
37. MASSAIA M, BORRIONE P, BATTAGLIO S et al.: Idiotype vaccination in human myeloma: generation of tumor-specific immune responses after high-dose chemotherapy. Blood (1999) 94:673-683.
38. GAHRTON G, TURA S, LJUNGMAN P et al.: Allogeneic bone marrow transplantation in multiple myeloma. N. Engl. J. Med. (1991) 325:1267-1273.
39. GAHRTON G, SVENSSON H, CAVO M et al.: Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983-93 and 1994-8 at European Group for Blood and Marrow Transplantation centres. Br. J. Haematol. (2001) 113:209-216.
40. ALYEA E, WELLER E, SCHLOSSMAN R et al.: T-cell-depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect. Blood (2001) 98:934-939.
41. BADROS A, BARLOGIE B, MORRIS C et al.: High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood (2001) 97:2574-2579.
42. KROGER N, SCHWERDTFEGER R, KIEHL M et al.: Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma. Blood (2002) 100:755-760.
43. RAJKUMAR SV, KYLE RA, GERTZ MA: Myeloma and the newly diagnosed patient: a focus on treatment and management. Semin. Oncol. (2002) 29:5-10.
44. BERENSON JR, HILLNER BE, KYLE RA et al.: American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J. Clin. Oncol. (2002) 20:3719-3736.
45. 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) 35:969-979.
46. MULLER GW, CORRAL LG, SHIRE MG et al.: Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J. Med. Chem. (1996) 39:3238-3240.
47. KENYON BM, BROWNE F, D'AMATO RJ: Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp. Eye Res. (1997) 64:971-978.
48. REIST M, CARRUPT PA, FRANCOTTE E, TESTA B: Chiral inversion and hydrolysis of thalidomide: mechanisms and catalysis by bases and serum albumin, and chiral stability of teratogenic metabolites. Chem. Res. Toxicol. (1998) 11:1521-1528.
49. ERIKSSON T, BJORKMAN S, ROTH B, FYGE A, HOGLUND P: Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide. Chirality (1995) 7:44-52.
50. HALES BF: Thalidomide on the comeback trail. Nat. Med. (1999) 5:489-490.
51. ZELDIS JB, WILLIAMS BA, THOMAS SD, ELSAYED ME: S.T.E.P.S: a comprehensive program for controlling and monitoring access to thalidomide. Clin. Ther. (1999) 21:319-330.
52. STIRLING DI: Thalidomide and its impact in dermatology. Semin. Cutan. Med. Surg. (1998) 17:231-242.
53. D'AMATO RJ, LOUGHMAN MS, FLYNN E, FOLKMAN J: Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. USA (1994) 91:4082-4085.
54. BAUER KS, DIXON SC, FIGG WD: Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem. Pharmacol. (1998) 55:1827-1834.
55. WU A, SCHEFFLER MR: Multi-dose phamacokinetics and safety of CC-5013 in 15 multiple myeloma patients. J. Clin. Oncol. (2004) 22:141s.
56. HIDESHIMA T, CHAUHAN D, SHIMA Y et al.: Thalidomide and its analogues overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood (2000) 96:2943-2950.
57. MITSIADES N, MITSIADES CS, POULAKI V et al.: Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood (2002) 99:4525-4530.
58. MULLER GW, CHEN R, HUANG SY et al.: Amino-substituted thalidomide analogs: potent inhibitors of TNF-α production. Bioorg. Med. Chem. Lett. (1999) 9:1625-1630.
59. FUJITA J, MESTRE JR, ZELDIS JB, SUBBARAMAIAH K, DANNENBERG AJ: Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2. Clin. Cancer Res. (2001) 7:3349-3355.
60. KEIFER JA, GUTTRIDGE DC, ASHBURNER BP, BALDWIN AS Jr: Inhibition of NF-κB activity by thalidomide through suppression of IκB kinase activity. J. Biol. Chem. (2001) 276:22382-22387.
61. ROWLAND TL, McHUGH SM, DEIGHTON J, EWAN PW, DEARMAN RJ, KIMBER I: Differential effect of thalidomide and dexamethasone on the transcription factor NF-κB. Int. Immunopharmacol. (2001) 1:49-61.
62. HIDESHIMA T, RICHARDSON P, CHAUHAN D et al.: The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. (2001) 61:3071-3076.
63. STEWART AK, SCANGA SE, ZHU YX, YAHYAPOUR M, MANOUKIAN A: Inhibition of Wnt pathway signaling by thalidomide and Revlimid™: studies in a Drosophila model system. Blood (2004) 104:916a.
64. CHAUHAN D, HIDESHIMA T, ROSEN S, REED JC, KHARBANDA S, ANDERSON KC: Apaf-1/cytochrome c independent and Smac dependent induction of apoptosis in multiple myeloma cells. J. Biol. Chem. (2001) 276:24453-24456.
65. RAJE N, KUMAR S, HIDESHIMA T et al.: Combination of the mTOR inhibitor rapamycin and Revlimid™ (CC-5013) has synergistic activity in multiple myeloma. Blood (2004) 104:4188-4193.
66. SINGHAL S, MEHTA J, DESIKAN R et al.: Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. (1999) 341:1565-1571.
67. LENTZSCH S, ROGERS MS, LE BLANC RJ et al.: S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice. Cancer Res. (2002) 62:2300-2305.
68. FUJITA K, ASAMI Y, TANAKA K, AKITA M, MERKER HJ: Anti-angiogenic effects of thalidomide: expression of apoptosis-inducible active-caspase-3 in a three-dimensional collagen gel culture of aorta. Histochem. Cell Biol. (2004) 122:27-33.
69. DAVIES FE, RAJE N, HIDESHIMA T et al.: Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood (2001) 98:210-216.
70. + T cells in vitro. J. Infect. Dis.(2003) 187(6):946-955.
71. LEBLANC R, HIDESHIMA T, CATLEY LP et al.: Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood (2004) 103:1787-1790.
72. HAYASHI T, HIDESHIMA T, AKIYAMA M et al.: Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br. J. Haematol. (2005) 128:192-203.
73. CORRAL LG, HASLETT PA, MULLER GW et al.: Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-α. J. Immunol. (1999) 163:380-386.
74. + cells in their blood. Immunopharmacology (2000) 46:175-179.
75. BARTLETT JB, DREDGE K, DALGLEISH AG: The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat. Rev. Cancer (2004) 4:314-322.
76. RICHARDSON P, JAGANNATH S, SCHLOSSMAN R et al.: A multi-center, randomized, Phase II study to evaluate the efficacy and safety of two CDC-5013 dose regimens when used alone or in combination with dexamethasone (Dex) for the treatment of relapsed or refractory multiple myeloma (MM). Blood (2002) 100:104a.
77. RICHARDSON PG, JAGANNATH S, HUSSEIN MA et al.: A multicenter, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide in subjects with relapsed and refractory multiple myeloma. Haematologica (2005) 90(Suppl. 1):154.
78. RAJKUMAR SV, HAYMAN SR, LACY MQ et al.: Combination therapy with CC-5013 (lenalidomide; Revlimid™) plus dexamethasone (Rev /Dex) for newly diagnosed myeloma (MM). Blood (2004) 106:4050-4053.
79. GIAGOUNIDIS AA, GERMING U, WAINSCOAT JS, BOULTWOOD J, AUL C: The 5q-syndrome. Hematology (2004) 9:271-277.
80. GIAGOUNIDIS AA, GERMING U, STRUPP C, HILDEBRANDT B, HEINSCH M, AUL C: Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup. Ann. Hematol. (2005) 84:569-571.
81. RICHARDSON PG, JAGANNATH S, SCHLOSSMAN R et al.: A multi-center, randomized, Phase II study to evaluate the efficacy and safety of 2 CDC-5013 dose regimens when used alone or in combination with dexamethasone (Dex) for the treatment of relapsed or refractory multiple myeloma (MM). Blood (2003) 102:235a.