Targeted therapy of multiple myeloma

Advances in Experimental Medicine and Biology

Volumn 779, Issue , 2013, Pages 197-221

  Dolloff, Nathan G ^a   Talamo, Giampaolo ^a  

^a PENN STATE CANCER INSTITUTE   (United States)

Author keywords

Clinical trials; Immunomodulatory agents; Molecular pathways; Multiple myeloma; Proteasome inhibitors; Targeted therapy

Indexed keywords

ACETYLSALICYLIC ACID; ACY 1215; AVE 1642; BORTEZOMIB; CARFILZOMIB; CYCLOPHOSPHAMIDE; DENOSUMAB; DEXAMETHASONE; DOXORUBICIN; FIGITUMUMAB; HISTONE DEACETYLASE INHIBITOR; HORMONE RECEPTOR; IMATINIB; IMMUNOMODULATING AGENT; LENALIDOMIDE; LOW MOLECULAR WEIGHT HEPARIN; MELPHALAN; PERIFOSINE; PHOSPHATIDYLINOSITOL 3 KINASE; POMALIDOMIDE; PREDNISONE; RETINOIC ACID; ROMIDEPSIN; SALINOSPORAMIDE A; SCATTER FACTOR; TANESPIMYCIN; THALIDOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT; WARFARIN;

ADVANCED CANCER; AUTOLOGOUS STEM CELL TRANSPLANTATION; BLOOD TOXICITY; BONE METASTASIS; BRADYCARDIA; CANCER GENETICS; CANCER RESISTANCE; CANCER SURVIVAL; CANCER THERAPY; CARCINOGENESIS; CHROMOSOME ABERRATION; CHRONIC MYELOID LEUKEMIA; CLINICAL EFFECTIVENESS; CONSOLIDATION CHEMOTHERAPY; CONSTIPATION; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SYNTHESIS; DRUG TARGETING; FATIGUE; FETUS MALFORMATION; HUMAN; HYPOTENSION; LETHARGY; MAINTENANCE THERAPY; MOLECULAR BIOLOGY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYALGIA; NEUROPATHY; NEUTROPENIA; NONHUMAN; OSTEOPOROSIS; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PROTEIN FAMILY; REVIEW; SEDATION; SIDE EFFECT; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA; TREATMENT RESPONSE; VENOUS THROMBOEMBOLISM;

EID: 84873598748     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4614-6176-0_9     Document Type: Review

References (116)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225-49.
2. Talamo G, Farooq U, Zangari M, et al. Beyond the CRAB symptoms: A study of presenting clinical manifestations of multiple myeloma. Clin Lymphoma Myeloma Leuk. 2010;10:464-8.
3. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-20.
4. Stewart AK, Richardson PG, San-Miguel JF. How I treat multiple myeloma in younger patients. Blood. 2009;114(27):5436-43.
5. Anderson KC, Alsina M, Bensinger W, et al. NCCN clinical practice guidelines in oncology: Multiple myeloma. J Natl Compr Canc Netw. 2009;7:908-42.
6. Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23:435-41.
7. Roodman GD, Dougall WC. RANK ligand as a therapeutic target for bone metastases and multiple myeloma. Cancer Treat Rev. 2008;34:92-101.
8. Berenson Jr. Therapeutic options in the management of myeloma bone disease. Semin Oncol. 2010;37 SUPPL1:S20-9.
9. Zangari M, Zhan F, Tricot G. Bone and paraproteinemias. Curr Opin Support Palliat Care. 2010;4:195-9.
10. Fenton JA, Pratt G, Rawstron AC, et al. Isotype class switching and the pathogenesis of m ultiple myeloma. Hematol Oncol. 2002;20:75-85.
11. Gonzalez D, van der Burg M, Garcia-Sanz R, et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood. 2007;110:3112-21.
12. Chesi M, Nardini E, Lim RS, et al. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood. 1998;92:3025-34.
13. He LZ, Tribioli C, Rivi R, et al. Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice. Proc Natl Acad Sci USA. 1997;94:5302-7.
14. Wong S, Witte ON. Modeling Philadelphia chromosome positive leukemias. Oncogene. 2001;20:5644-59.
15. Fiancette R, Amin R, Truffinet V, et al. A myeloma translocation-like model associating CCND1 with the immunoglobulin heavy-chain locus 3 ¢ enhancers does not promote by itself B-cell malignancies. Leuk Res. 2010;34:1043-51.
16. Rasmussen T, Theilgaard-Monch K, Hudlebusch HR, et al. Occurrence of dysregulated oncogenes in primary plasma cells representing consecutive stages of myeloma pathogenesis: Ndications for different disease entities. Br J Haematol. 2003;123:253-62.
17. Nahi H, Sutlu T, Jansson M, et al. Clinical impact of chromosomal aberrations in multiple myeloma. J Intern Med. 2011;269:137-47.
18. Chang H, Qi C, Yi QL, et al. p53 Gene deletion detected by fl uorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood. 2005;105:358-60.
19. Knight R. IMiDs: A novel class of immunomodulators. Semin Oncol. 2005;32:S24-30.
20. Palumbo A, Facon T, Sonneveld P, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood. 2008;111:3968-77.
21. Paravar T, Lee DJ. Thalidomide: Mechanisms of action. Int Rev Immunol. 2008;27:111-35.
22. Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345-50.
23. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133-42.
24. Gay F, Hayman SR, Lacy MQ, et al. Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: A comparative analysis of 411 patients. Blood. 2010;115:1343-50.
25. Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010;24:1934-9.
26. Obeng EA, Carlson LM, Gutman DM, et al. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107:4907-16.
27. Cenci S, Mezghrani A, Cascio P, et al. Progresively impaired proteasomal capacity during terminal plasma cell differentiation. EMBO J. 2006;25:1104-13.
28. Chauhan D, Hideshima T, Anderson KC. Targeting proteasomes as therapy in multiple myeloma. Adv Exp Med Biol. 2008;615:251-60.
29. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609-17.
30. Kuhn DJ, Chen Q, Voorhees PM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007;110:3281-90.
31. O'Connor OA, Stewart AK, Vallone M, et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009;15:7085-91.
32. Singh AV, Palladino MA, Lloyd GK, et al. Pharmacodynamic and efficacy studies of the novel proteasome inhibitor NPI-0052 (marizomib) in a human plasmacytoma xenograft murine model. Br J Haematol. 2010;149:550-9.
33. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone co mbination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-86.
34. Kim TY, Bang YJ, Robertson KD. Histone deacetylase inhibitors for cancer therapy. Epigenetics. 2006;1:14-23.
35. Kikuchi J, Wada T, Shimizu R, et al. Histone deacetylases are critical targets of bortezomibinduced cytotoxicity in multiple myeloma. Blood. 2010;116:406-17.
36. Richardson P, Mitsiades C, Colson K, et al. Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. Leuk Lymphoma. 2008;49:502-7.
37. Badros A, Burger AM, Philip S, et al. Phase I study of vorinostat in combination with bortezomib for relapsed and refractory multiple myeloma. Clin Cancer Res. 2009;15:5250-7.
38. Mazumder A, Vesole DH, Jagannath S. Vorinostat plus bortezomib for the treatment of relapsed/refractory multiple myeloma: A case series illustrating utility in clinical practice. Clin Lymphoma Myeloma Leuk. 2010;10:149-51.
39. Niesvizky R, Ely S, Mark T, et al. Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma. Cancer. 2011;117:336-42.
40. Santo L, Hideshima T, Kung AL, Tseng JC, Tang D, Yang M, et al. Preclinical activity, pharmacodynamic and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood. 2012;19:2579-89. Epub ahead of print
41. Davenport EL, Moore HE, Dunlop AS, et al. Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Blood. 2007;110:2641-9.
42. Mitsiades CS, Mitsiades NS, McMullan DJ, et al. Antimyeloma activity of heat shock protein- 90 inhibition. Blood. 2006;107:1092-100.
43. Okawa Y, Hideshima T, Steed P, et al. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009;113:846-55.
44. Richardson PG, Chanan-Khan AA, Alsina M, et al. Tanespimycin monotherapy in relapsed multiple myeloma: Results of a phase 1 dose-escalation study. Br J Haematol. 2010;150:438-45.
45. Richardson PG, Badros AZ, Jagannath S, et al. Tanespimycin with bortezomib: Activity in relapsed/refractory patients with multiple myeloma. Br J Haematol. 2010;150:428-37.
46. Kumar S, Lacy MQ, Dispenzieri A, et al. Single agent dexamethasone for pre-stem cell transplant induction therapy for multiple myeloma. Bone Marrow Transplant. 2004;34:485-90.
47. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: The second decade. Cell. 1995;83:835-9.
48. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8:627-44.
49. Pene F, Claessens YE, Muller O, et al. Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma. Oncogene. 2002;21:6587-97.
50. Stromberg T, Dimberg A, Hammarberg A, et al. Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone. Blood. 2004;103:3138-47.
51. Frost P, Moatamed F, Hoang B, et al. In vivo antitumor effects of the mTOR inhibitor CCI- 779 against human multiple myeloma cells in a xenograft model. Blood. 2004;104:4181-7.
52. Yan H, Frost P, Shi Y, et al. Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Cancer Res. 2006;66:2305-13.
53. Francis LK, Alsayed Y, Leleu X, et al. Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-Allylamino-17- demethoxygeldanamycin has synergistic activity in multiple myeloma. Clin Cancer Res. 2006;12:6826-35.
54. Raje N, Kumar S, Hideshima T, et al. Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Blood. 2004;104:4188-93.
55. Harvey RD, Lonial S. PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma. Future Oncol. 2007;3:639-47.
56. Farag SS, Zhang S, Jansak BS, et al. Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma. Leuk Res. 2009;33:1475-80.
57. Georgii-Hemming P, Wiklund HJ, Ljunggren O, et al. Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines. Blood. 1996;88:2250-8.
58. Ge NL, Rudikoff S. Insulin-like growth factor I is a dual effector of multiple myeloma cell growth. Blood. 2000;96:2856-61.
59. Lacy MQ, Alsina M, Fonseca R, et al. Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 receptor monoclonal antibody CP-751,871 in patients with multiple myeloma. J Clin Oncol. 2008;26:3196-203.
60. Moreau P, Cavallo F, Leleu X, Hulin C, Amiot M, Descamps G, Facon T, Boccadoro M, Mignard D, Harousseau JL. Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma. Leukemia. 2011;25(5):872-4.
61. Borset M, Hjorth-Hansen H, Seidel C, et al. Hepatocyte growth factor and its receptor c-met in multiple myeloma. Blood. 1996;88:3998-4004.
62. Derksen PW, de Gorter DJ, Meijer HP, et al. The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia. 2003;17:764-74.
63. Hov H, Holt RU, Rø TB, Fagerli UM, Hjorth-Hansen H, Baykov V, Christensen JG, Waage A, Sundan A, Børset M. A selective c-met inhibitor blocks an autocrine hepatocyte growth Targeted Therapy of Multiple Myeloma 219 factor growth loop in ANBL-6 cells and prevents migration and adhesion of myeloma cells. Clin Cancer Res. 2004;10(19):6686-94.
64. Maloney DG, Donovan K, Hamblin TJ. Antibody therapy for treatment of multiple myeloma. Semin Hematol. 1999;36:30-3.
65. Kapoor P, Greipp PT, Morice WG, et al. Anti-CD20 monoclonal antibody therapy in multiple myeloma. Br J Haematol. 2008;141:135-48.
66. Zojer N, Kirchbacher K, Vesely M, et al. Rituximab treatment provides no clinical benefit in patients with pretreated advanced multiple myeloma. Leuk Lymphoma. 2006;47:1103-9.
67. Moreau P, Voillat L, Benboukher L, et al. Rituximab in CD20 positive multiple myeloma. Leukemia. 2007;21:835-6.
68. Kovalchuk AL, Kim JS, Park SS, et al. IL-6 transgenic mouse model for extraosseous plasmacytoma. Proc Natl Acad Sci U S A. 2002;99:1509-14.
69. van Rhee F, Fayad L, Voorhees P, et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol. 2010;28:3701-8.
70. Hunsucker SA, Magarotto V, Kuhn DJ, et al. Blockade of interleukin-6 signaling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma. Br J Haematol. 2011;152:579-92.
71. Voorhees PM, Chen Q, Small GW, et al. Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. Br J Haematol. 2009;145:481-90.
72. Fulciniti M, Hideshima T, Vermot-Desroches C, et al. A high-Affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma. Clin Cancer Res. 2009;15:7144-52.
73. van Rhee F, Szmania SM, Dillon M, et al. Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma. Mol Cancer Ther. 2009;8:2616-24.
74. Lesage D, Troussard X, Sola B. The enigmatic role of cyclin D1 in multiple myeloma. Int J Cancer. 2005;115:171-6.
75. Marsaud V, Tchakarska G, Andrieux G, et al. Cyclin K and cyclin D1b are oncogenic in myeloma cells. Mol Cancer. 2010;9:103.
76. Tchakarska G, Le Lan-Leguen A, Roth L, et al. The targeting of the sole cyclin D1 is not adequate for mantle cell lymphoma and myeloma therapies. Haematologica. 2009;94:1781-2.
77. Raje N, Hideshima T, Mukherjee S, et al. Preclinical activity of P276-00, a novel smallmolecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma. Leukemia. 2009;23:961-70.
78. Dispenzieri A, Gertz MA, Lacy MQ, et al. Flavopiridol in patients with relapsed or refractory multiple myeloma: A phase 2 trial with clinical and pharmacodynamic end-points. Haematologica. 2006;91:390-3.
79. Holkova B, Perkins EB, Ramakrishnan V, Tombes MB, Shrader E, Talreja N, Wellons MD, Hogan KT, Roodman GD, Coppola D, Kang L, Dawson J, Stuart RK, Peer C, Figg Sr WD, Kolla S, Doyle A, Wright J, Sullivan DM, Roberts JD, Grant S. Phase I trial of bortezomib (PS-341; NSC 681239) and alvocidib ( fl avopiridol; NSC 649890) in patients with recurrent or refractory B-cell neoplasms. Clin Cancer Res. 2011;17(10):3388-97.
80. Saunders A, Core LJ, Lis JT. Breaking barriers to transcription elongation. Nat Rev Mol Cell Biol. 2006;7:557-67.
81. Tong WG, Chen R, Plunkett W, Siegel D, Sinha R, Harvey RD, Badros AZ, Popplewell L, Coutre S, Fox JA, Mahadocon K, Chen T, Kegley P, Hoch U, Wierda WG. Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma. J Clin Oncol. 2010;28(18):3015-22.
82. Santo L, Vallet S, Hideshima T, Cirstea D, Ikeda H, Pozzi S, Patel K, Okawa Y, Gorgun G, Perrone G, Calabrese E, Yule M, Squires M, Ladetto M, Boccadoro M, Richardson PG, Munshi NC, Anderson KC, Raje N. AT7519, a novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma. Oncogene. 2010;29(16):2325-36.
83. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Ghobrial IM, Richardson PG, Young RA, Hahn WC, Anderson KC, Kung AL, Bradner JE, Mitsiades CS. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904-17.
84. Santra M, Zhan F, Tian E, et al. A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood. 2003;101:2374-6.
85. Quintero-Rivera F, El-Sabbagh Badr R, Rao PN. FGFR3 amplification in the absence of IGHFGFR3 fusion t(4;14) in myeloma. Cancer Genet Cytogenet. 2009;195:92-3.
86. Krejci P, Murakami S, Prochazkova J, et al. NF449 is a novel inhibitor offibroblast growth factor receptor 3 (FGFR3) signaling active in chondrocytes and multiple myeloma cells. J Biol Chem. 2010;285:20644-53.
87. Xin X, Abrams TJ, Hollenbach PW, et al. CHIR-258 is efficacious in a newly developedfibroblast growth factor receptor 3-expressing orthotopic multiple myeloma model in mice. Clin Cancer Res. 2006;12:4908-15.
88. Trudel S, Stewart AK, Rom E, et al. The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells. Blood. 2006;107:4039-46.
89. Matsui W, Wang Q, Barber JP, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008;68:190-7.
90. Huff CA, Matsui W. Multiple myeloma cancer stem cells. J Clin Oncol. 2008;26:2895-900.
91. Mueller MM, Fusenig NE. Friends or foes - Bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004;4:839-49.
92. McMillin DW, Delmore J, Weisberg E, Negri JM, Geer DC, Klippel S, Mitsiades N, Schlossman RL, Munshi NC, Kung AL, Griffin JD, Richardson PG, Anderson KC, Mitsiades CS. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med. 2010;16(4):483-9.
93. Rajkumar SV, Mesa RA, Fonseca R, et al. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res. 2002;8:2210-6.
94. Ria R, Roccaro AM, Merchionne F, et al. Vascular endothelial growth factor and its receptors in multiple myeloma. Leukemia. 2003;17:1961-6.
95. Kumar S, Witzig TE, Timm M, et al. Expression of VEGF and its receptors by myeloma cells. Leukemia. 2003;17:2025-31.
96. Van Meter ME, Kim ES. Bevacizumab: Current updates in treatment. Curr Opin Oncol. 2010;22:586-91.
97. Zangari M, Anaissie E, Stopeck A, et al. Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma. Clin Cancer Res. 2004;10:88-95.
98. Kovacs MJ, Reece DE, Marcellus D, et al. A phase II study of ZD6474 (zactima, a selective inhibitor of VEGFR and EGFR tyrosine kinase in patients with relapsed multiple myeloma-NCIC CTG IND 145. Invest New Drugs. 2006;24:529-35.
99. Prince HM, Honemann D, Spencer A, et al. Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: A phase 2 study of pazopanib (GW786034). Blood. 2009;113:4819-20.
100. Alsina M, Fonseca R, Wilson EF, et al. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Blood. 2004;103:3271-7.
101. Chanan-Khan AA, Niesvizky R, Hohl RJ, et al. Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma. Leuk Lymphoma. 2009;50:559-65.
102. Tsimberidou AM, Waddelow T, Kantarjian HM, et al. Pilot study of recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein (TNFR:Fc; Enbrel) in patients with refractory multiple myeloma: Increase in plasma TNF alpha levels during treatment. Leuk Res. 2003;27:375-80.
103. Dispenzieri A, Gertz MA, Lacy MQ, Geyer SM, Greipp PR, Rajkumar SV, Kimlinger T, Lust JA, Fonseca R, Allred J, Witzig TE. A phase II trial of imatinib in patients with refractory/relapsed myeloma. Leuk Lymphoma. 2006;47(1):39-42.
104. Chapman MA, Lawrence MS, Keats JJ, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467-72.
105. Barlogie B, Desikan R, Eddlemon P, 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;98:492-4.
106. Mileshkin L, Biagi JJ, Mitchell P, et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: Adverse prognostic impact of advanced age. Blood. 2003;102:69-77.
107. Tosi P, Zamagni E, Cellini C, et al. Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma. Haematologica. 2002;87:408-14.
108. Rajkumar SV, Gertz MA, Lacy MQ, et al. Thalidomide as initial therapy for early-stage myeloma. Leukemia. 2003;17:775-9.
109. Rajkumar SV, Blood E, Vesole D, et al. 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;24:431-6.
110. Richardson P, Jagannath S, Hussein M, et al. Safety and efficacy of single-Agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood. 2009;114:772-8.
111. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123-32.
112. Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: An open-label randomized controlled trial. Lancet Oncol. 2010;11:29-37.
113. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487-98.
114. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol. 2005;129:776-83.
115. Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: Combination therapy improves time to progression. J Clin Oncol. 2007;25:3892-901.
116. Mikhael JR, Belch AR, Prince HM, et al. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: Results of a global phase 3b expanded access program. Br J Haematol. 2009;144:169-75.