Contemporary drug therapies for multiple myeloma

Drugs of Today

Volumn 49, Issue 9, 2013, Pages 563-573

  De La Puente, P ^a   Azab, Abdel Kareem ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Monoclonal antibodies; Multiple myeloma; Therapeutic strategies; Tumor microenvironment

Indexed keywords

BORTEZOMIB; BT 062; CARFILZOMIB; DARATUMUMAB; DEXAMETHASONE; ELOTUZUMAB; IMMUNOMODULATING AGENT; IXAZOMIB CITRATE; LENALIDOMIDE; MONOCLONAL ANTIBODY; PLERIXAFOR; POMALIDOMIDE; PROTEASOME INHIBITOR; RIVIPANSEL; SALINOSPORAMIDE; SALINOSPORAMIDE A; SELECTIN ANTAGONIST; SILTUXIMAB; THALIDOMIDE; UNCLASSIFIED DRUG;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BIRTH DEFECT; BLOOD TOXICITY; BONE ATROPHY; BONE MARROW; BONE MARROW SUPPRESSION; CELL ADHESION; CELL CYCLE ARREST; CELL CYCLE REGULATION; CELL HOMING; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CONSTIPATION; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DIGESTIVE SYSTEM FUNCTION DISORDER; DNA DAMAGE; DOWN REGULATION; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; FATIGUE; HEMATOLOGIC MALIGNANCY; HUMAN; IN VITRO STUDY; INFECTION; LYMPHOCYTE PROLIFERATION; MONOTHERAPY; MULTICENTER STUDY (TOPIC); MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NEUROPATHY; OPTIMAL DRUG DOSE; OSTEOCLASTOGENESIS; OUTCOME ASSESSMENT; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REVIEW; SEDATION; SIDE EFFECT; SKIN MANIFESTATION; TERATOGENICITY; THROMBOCYTOPENIA; THROMBOEMBOLISM; THROMBOSIS; TREATMENT RESPONSE; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR REGRESSION; TUMOR VOLUME;

EID: 84885210510     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2013.49.09.2020941     Document Type: Review

References (88)

1. Ludwig, H. Advances in biology and treatment of multiple myeloma. Ann Oncol 2005, 16(Suppl. 2): ii106-12. (Pubitemid 40908944)
2. Kyle, R.A., Gertz, M.A., Witzig, T.E. et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003, 78(1): 21-33. (Pubitemid 36033957)
3. 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. (Pubitemid 16080597)
4. 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. (Pubitemid 14149087)
5. Gertz, M.A., Kalish, L.A., Kyle, R.A., Hahn, R.G., Tormey, D.C., Oken, M.M. Phase III study comparing vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) chemotherapy with VAD plus recombinant interferon alfa-2 in refractory or relapsed multiple myeloma. An Eastern Cooperative Oncology Group study. Am J Clin Oncol 1995, 18(6): 475-80. (Pubitemid 26004052)
6. Alexanian, R., Barlogie, B., Dixon, D. High-dose glucocorticoid treatment of resistant myeloma. Ann Intern Med 1986, 105(1): 8-11. (Pubitemid 16097913)
7. Kumar, S.K., Rajkumar, S.V., Dispenzieri, A. et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008, 111(5): 2516-20.
8. Mitsiades, C.S., Hayden, P.J., Anderson, K.C., Richardson, P.G. From the bench to the bedside: emerging new treatments in multiple myeloma. Best Pract Res Clin Haematol 2007, 20(4): 797-816. (Pubitemid 350215385)
9. Dimopoulos, M., Spencer, A., Attal, M. et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007, 357(21): 2123-32. (Pubitemid 350146107)
10. Richardson, P.G., Sonneveld, P., Schuster, M.W. et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005, 352(24): 2487-98. (Pubitemid 41007864)
11. Blade, J., Cibeira, M.T., Rosinol, L. Novel drugs for the treatment of multiple myeloma. Haematologica 2010, 95(5): 702-4.
12. Crane, E., List, A. Immunomodulatory drugs. Cancer Invest 2005, 23(7): 625-34. (Pubitemid 43286664)
13. Vacca, A., Ribatti, D., Roccaro, A.M., Frigeri, A., Dammacco, F. Bone marrow angiogenesis in patients with active multiple myeloma. Semin Oncol 2001, 28(6): 543-50. (Pubitemid 33134413)
14. Ito, T., Ando, H., Suzuki, T. et al. Identification of a primary target of thalidomide teratogenicity. Science 2010, 327(5971): 1345-50.
15. Zhu, Y.X., Braggio, E., Shi, C.X. et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 2011, 118(18): 4771-9.
16. Dimopoulos, M.A., Richardson, P.G., Brandenburg, N., Yu, Z., Weber, D.M., Niesvizky, R., Morgan, G.J. A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 2012, 119(12): 2764-7.
17. Thomas, A., Mailankody, S., Korde, N., Kristinsson, S.Y., Turesson, I., Landgren, O. Second malignancies after multiple myeloma: from 1960s to 2010s. Blood 2012, 119(12): 2731-7.
18. D'Amato, R.J., Loughnan, M.S., Flynn, E., Folkman, J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 1994, 91(9): 4082-5. (Pubitemid 24139577)
19. Davies, F.E., Raje, N., Hideshima, T. et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001, 98(1): 210-6.
20. Mitsiades, N., Mitsiades, C.S., Poulaki, V. et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002, 99(12): 4525-30. (Pubitemid 34627223)
21. Teo, S.K., Properties of thalidomide and its analogues: implications for anticancer therapy. AAPS J 2005, 7(1): E14-9. (Pubitemid 41554303)
22. Singhal, S., Mehta, J., Desikan, R. et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999, 341(21): 1565-71.
23. 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(2): 492-4.
24. Dimopoulos, M.A., Zervas, K., Kouvatseas, G. et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol 2001, 12(7): 991-5. (Pubitemid 32725775)
25. Lee, C.K., Barlogie, B., Munshi, N. et al. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003, 21(14): 2732-9. (Pubitemid 46606319)
26. Glasmacher, A., Hahn, C., Hoffmann, F. 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. (Pubitemid 43381591)
27. Dimopoulos, M.A., Eleutherakis-Papaiakovou, V. Adverse effects of thalidomide administration in patients with neoplastic diseases. Am J Med 2004, 117(7): 508-15. (Pubitemid 39349589)
28. Richardson, P., Anderson, K. Immunomodulatory analogs of thalidomide: an emerging new therapy in myeloma. J Clin Oncol 2004, 22(16): 3212-4. (Pubitemid 41103674)
29. Davies, F., Baz, R. Lenalidomide mode of action: linking bench and clinical findings. Blood Reviews 2010, 24(Suppl. 1): S13-19.
30. Richardson, P.G., Schlossman, R.L., Weller, E. et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002, 100(9): 3063-7. (Pubitemid 35217050)
31. Richardson, P.G., Blood, E., Mitsiades, C.S. et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006, 108(10): 3458-64.
32. Rajkumar, S.V., Hayman, S.R., Lacy, M.Q. et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005, 106(13): 4050-3. (Pubitemid 41775908)
33. Richardson, P.G., Jagganath, D.E., Avigan, M. et al. Lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): final results of a multicenter phase 1 trial. Blood (ASH Annu Meet Abst) 2006, 108(11): 405.
34. Verhelle, D., Corral, L.G., Wong, K. et al. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res 2007, 67(2): 746-55. (Pubitemid 46192215)
35. Anderson, G., Gries, M., Kurihara, N. et al. Thalidomide derivative CC-4047 inhibits osteoclast formation by downregulation of PU.1. Blood 2006, 107(8): 3098-105.
36. Schey, S.A., Fields, P., Bartlett, J.B. et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004, 22(16): 3269-76. (Pubitemid 41103682)
37. Lacy, M.Q., Hayman, S.R., Gertz, M.A. et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 2009, 27(30): 5008-14.
38. Lacy, M.Q., Allred, J.B., Gertz, M.A. et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 2011, 118(11): 2970-5.
39. Lacy, M.Q., Hayman, S.R., Gertz, M.A. et al. Pomalidomide (CC4047) plus low-dose dexamethasone (Pom/dex) is highly effective therapy in relapsed multiple myeloma. Blood (ASH Annu Meet Abst) 2008, 112(11): 866.
40. Adams, J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 2004, 4(5): 349-60. (Pubitemid 38579481)
41. McConkey, D.J., Zhu, K. Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist Updat 2008, 11(4-5): 164-79.
42. Murakawa, Y., Sonoda, E., Barber, L.J. et al. Inhibitors of the proteasome suppress homologous DNA recombination in mammalian cells. Cancer Res 2007, 67(18): 8536-43. (Pubitemid 47437428)
43. Jacquemont, C., Taniguchi, T. Proteasome function is required for DNA damage response and Fanconi anemia pathway activation. Cancer Res 2007, 67(15): 7395-405. (Pubitemid 47206570)
44. Mitsiades, N., Mitsiades, C.S., Poulaki, V. et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci U S A 2002, 99(22): 14374-9. (Pubitemid 35257679)
45. Hideshima, T., Richardson, P., Chauhan, D., Palombella, V.J., Elliott, P.J., Adams, J., Anderson, K.C. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001, 61(7): 3071-6. (Pubitemid 32691956)
46. Orlowski, R.Z., Stinchcombe, T.E., Mitchell, B.S. et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol 2002, 20(22): 4420-7. (Pubitemid 35334752)
47. Richardson, P.G., Barlogie, B., Berenson, J. et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003, 348(26): 2609-17. (Pubitemid 36741588)
48. Demo, S.D., Kirk, C.J., Aujay, M.A. et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res 2007, 67(13): 6383-91. (Pubitemid 47037522)
49. Chauhan, D., Catley, L., Li, G. et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from bortezomib. Cancer Cell 2005, 8(5): 407-19. (Pubitemid 41579835)
50. Vij, R., Wang, M., Kaufman, J.L. et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood 2012, 119(24): 5661-70.
51. Vij, R., Kaufman, J.L., Jakubowiak, A.J. et al. Final results from the bortezomib-naive group of PX-171-004, a phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory MM. Blood (ASH Annu Meet Abst) 2011, 118(21): 813.
52. Shah, J.J., Stadtmauer, E.A., Abonour, R. et al. A multi-center phase I/II trial of carfilzomib and pomalidomide with dexamethasone (Car-Pom-d) in patients with relapsed/refractory multiple myeloma. Blood (ASH Annu Meet Abst) 2012, 120(21): 74.
53. Sonneveld, P., Asselbergs, E., Zweegman, S. et al. Carfilzomib combined with thalidomide and dexamethasone (CTD) is an highly effective induction and consolidation treatment in newly diagnosed patients with multiple myeloma (MM) who are transplant candidate. Blood (ASH Annu Meet Abst) 2012, 120(21): 333.
54. Siegel, D.S., Wang, M., Martin, T.G. et al. A phase 2 study of prolonged carfilzomib therapy in patients with multiple myeloma previously enrolled in carfilzomib clinical trials. Blood (ASH Annu Meet Abst) 2012, 120(21): 2962.
55. Obaidat, A., Weiss, J., Wahlgren, B. et al. Proteasome regulator marizomib (NPI-0052) exhibits prolonged inhibition, attenuated efflux, and greater cytotoxicity than its reversible analogs. J Pharmacol Exp Ther 2011, 337(2): 479-86.
56. Richardson, P., Hofmeister, C.C., Zimmerman, T.M. et al. Phase 1 clinical trial of NPI-0052, a novel proteasome inhibitor in patients with multiple myeloma. Blood (ASH Annu Meet Abst) 2008, 112(11): 2770.
57. Chauhan, D., Tian, Z., Zhou, B. et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res 2011, 17(16): 5311-21.
58. Kumar, S., Bensinger, W.I., Reeder, C.B. et al. Weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients with relapsed and/or refractory multiple myeloma: results from a phase 1 dose-escalation study. Blood (ASH Annu Meet Abst) 2011, 118(21): 816.
59. Salles, G., Seymour, J.F., Offner, F. et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011, 377(9759): 42-51.
60. Kumaresan, P.R., Lai, W.C., Chuang, S.S., Bennett, M., Mathew, P.A. CS1, a novel member of the CD2 family, is homophilic and regulates NK cell function. Mol Immunol 2002, 39(1-2): 1-8. (Pubitemid 35245377)
61. Jakubowiak, A.J., Benson, D.M., Bensinger, W. et al. Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma. J Clin Oncol 2012, 30(16): 1960-5.
62. Lonial, S., Vij, R., Harousseau, J.L. et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 2012, 30(16): 1953-9.
63. Zonder, J.A., Mohrbacher, A.F., Singhal, S. et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 2012, 120(3): 552-9.
64. Lauta, V.M. Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data. Cytokine 2001, 16(3): 79-86. (Pubitemid 34081699)
65. Voorhees, P.M., Manges, R.F., Sonneveld, P. et al. A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Br J Haematol 2013, 161(3): 357-66.
66. Voorhees, P.M., Manges, R.F., Sonneveld, P. et al. A phase 2 multicenter study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Blood (ASH Annu Meet Abst) 2011, 118(21): 3971.
67. Chillemi, A., Zaccarello, G., Quarona, V. et al. Anti-CD38 antibody therapy: windows of opportunity yielded by the functional characteristics of the target molecule. Mol Med 2013, 19: 99-108.
68. de Weers, M., Tai, Y.T., van der Veer, M.S. et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 2011, 186(3): 1840-8.
69. Plesner, T., Lokhorst, H., Gimsing, P., Nahi, H., Lisby, S., Richardson, P.G. Daratumumab, a CD38 monoclonal antibody in patients with multiple myeloma - data from a dose-escalation phase I/II study. Blood (ASH Annu Meet Abst) 2012, 120(21): 73.
70. Sanderson, R.D., Lalor, P., Bernfield, M. B lymphocytes express and lose syndecan at specific stages of differentiation. Cell Regul 1989, 1(1): 27-35.
71. Ikeda, H., Hideshima, T., Fulciniti, M. et al. The monoclonal antibody nBT062 conjugated to cytotoxic maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res 2009, 15(12): 4028-37.
72. Heffner, L.T., Jagannath, S., Zimmerman, T.M. et al. BT062, an antibody-drug conjugate directed against CD138, given weekly for 3 weeks in each 4 week cycle: safety and further evidence of clinical activity. Blood (ASH Annu Meet Abst) 2012, 120(21): 4042.
73. McMillin, D.W., Delmore, J., Weisberg, E. et al. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med 2010, 16(4): 483-9.
74. Azab, A.K., Azab, F., Blotta, S. et al. RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood 2009, 114(3): 619-29.
75. Azab, A.K., Hu, J., Quang, P. et al. Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features. Blood 2012, 119(24): 5782-94.
76. Azab, A.K., Quang, P., Azab, F. et al. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood 2012, 119(6): 1468-78.
77. Azab, A.K., Runnels, J.M., Pitsillides, C. et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 2009, 113(18): 4341-51.
78. Azab, A.K., Azab, F., Quang, P. et al. Dissecting the role of CXCR7 in cell trafficking of endothelial-cells and endothelial-progenitor-cells in multiple myeloma. Blood (ASH Annu Meet Abst) 2011, 118(21): 3934.
79. Azab, F., Azab, A.K., Maiso, P. et al. The role of PI3K signaling in cell trafficking of multiple myeloma. Blood (ASH Annu Meet Abst) 2011, 118(21): 1804.
80. Neri, P., Bahlis, N.J. Targeting of adhesion molecules as a therapeutic strategy in multiple myeloma. Curr Cancer Drug Targets 2012, 12(7): 776-96.
81. Ngo, H.T., Leleu, X., Lee, J. et al. SDF-1/CXCR4 and VLA-4 interaction regulates homing in Waldenstrom macroglobulinemia. Blood 2008, 112(1): 150-8.
82. Uchiyama, H., Barut, B.A., Chauhan, D., Cannistra, S.A., Anderson, K.C. Characterization of adhesion molecules on human myeloma cell lines. Blood 1992, 80(9): 2306-14.
83. Jacobsen, K., Kravitz, J., Kincade, P.W., Osmond, D.G. Adhesion receptors on bone marrow stromal cells: in vivo expression of vascular cell adhesion molecule-1 by reticular cells and sinusoidal endothelium in normal and gamma-irradiated mice. Blood 1996, 87(1): 73-82. (Pubitemid 26011822)
84. Mori, Y., Shimizu, N., Dallas, M. et al. Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis. Blood 2004, 104(7): 2149-54. (Pubitemid 39297870)
85. Olson, D.L., Burkly, L.C., Leone, D.R., Dolinski, B.M., Lobb, R.R. Anti-alpha4 integrin monoclonal antibody inhibits multiple myeloma growth in a murine model. Mol Cancer Ther 2005, 4(1): 91-9. (Pubitemid 40268070)
86. Neri, P., Ren, L., Azab, A.K. et al. Integrin 7-mediated regulation ot multiple myeloma cell adhesion, migration, and invasion. Blood 2011, 117(23): 6202-13.
87. Juarez, J., Bendall, L. SDF-1 and CXCR4 in normal and malignant hematopoiesis. Histol Histopathol 2004, 19(1): 299-309. (Pubitemid 38111273)
88. Alsayed, Y., Ngo, H., Runnels, J. et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood 2007, 109(7): 2708-17. (Pubitemid 46482062)