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Pomalidomide for the treatment of relapsed–refractory multiple myeloma: a review of biological and clinical data

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References

  • Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011;364:1046-60
  • Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer 2012;12:335-48
  • Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. Ca Cancer J Clin 2014;64:9-29
  • Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-403
  • Ludwig H, Beksac M, Blade J, et al. Current multiple myeloma treatment strategies with novel agents: a European perspective. Oncologist 2010;15:6-25
  • Petrucci MT, Giraldo P, Corradini P, et al. A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma. Br J Haematol 2013;160:649-59
  • Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDS and bortezomib: a multicenter international myeloma working group study. Leukemia 2012;26:149-57
  • Anderson KC. Targeted therapy of multiple myeloma based upon tumor-microenvironmental interactions. Exp Hematol 2007;35(4 suppl 1):155-62
  • Zonder JA, Mohrbacher AF, Singhal S, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 2012;120:552-9
  • Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 2012;30:1953-9
  • Jakubowiak A, Berenson DM, 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;30:1960-5
  • Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood 2013;122:2331-7
  • San-Miguel JF, Richardson PG, Gunther A, et al. Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma. J Clin Oncol 2013;31:3696-703
  • Berenson JR, Hilger JD, Yellin O, et al. A phase 1/2 study of oral panobinostat combined with melphalan for patients with relapsed or refractory multiple myeloma. Ann Hematol 2014;93:89-98
  • Dimopoulos M, Siegel DS, Lonial S, et al. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol 2013;14:1129-40
  • Orlowski RZ. Novel agents for multiple myeloma to overcome resistance in phase III clinical trials. Semin Oncol 2013;5:634-51
  • Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapse and refractory multiple myeloma. Blood 2012;120:2817-25
  • Niesvizky R, Martin TG, Bensinger WI, et al. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Clin Cancer Res 2013;19:2248-56
  • Wang M, Martin T, Bensinger W, et al. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood 2013;122:3122-8
  • Mitsiades CS, Chen-Kiang S. Immunomodulation as a therapeutic strategy in the treatment of multiple myeloma. Crit Rev Oncol Hematol 2013;88:S5-13
  • FDA US Food and Drug Administration (FDA). Available from: www.fda.gov/
  • European Medicines Agency (EMA). Science Medicines health. Available from: www.wma.europa.eu
  • 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;39:3238-40
  • Hoffmann M, Kasserra C, Reyes J, et al. Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration. Cancer Chemother Pharmacol 2013;71:489-501
  • Matous J, Siegel DS, Duong HK, et al. MM-008: a phase 1 trial evaluating pharmacokinetics and tolerability of pomalidomide + low dose dexamethasone in patients with relapsed/refractory multiple myeloma and renal impairment [abstract 5393]. ASH Annual Meeting Abstracts; 2013
  • Schey S, Ramasamy K. Pomalidomide therapy for myeloma. Expert Opin Investig Drugs 2011;117:691-700
  • Hideshima T, Chauhan D, Shima Y, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000;96:2943-50
  • Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99:4525-30
  • Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 2009;27:5008-14
  • Richardson PG, Hofmeister CC, Siegel D, et al. MM-005: a phase 1 trial of pomalidomide, bortezomib, and low-dose dexamethasone (PVD) in relapsed and/or refractory multiple myeloma (RRMM) [abstract 1969]. ASH Annual Meeting Abstracts; 2013
  • Gupta D, Treon SP, Shima Y, et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia 2001;15:1950-61
  • Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDs) in multiple myeloma. Leukemia 2010;24:22-32
  • Görgün G, Calabrese E, Soydan E, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 2010;116:3227-37
  • Galustian C, Meyer B, Labarthe MC, et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother 2009;58:1033-45
  • Schey SA, Fields P, Bartlett JB, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004;22:3269-76
  • Anderson G, Gries M, Kurihara N, et al. Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood 2006;107:3098-105
  • Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 2011;118:4771-9
  • Lopez-Girona A, Mendy D, Ito T, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia 2012;26:2326-35
  • Broyl A, Kuiper R, van Duin M, et al. High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance. Blood 2013;121:624-7
  • Thakurta A, Gandhi AK, Waldman M, et al. Absence of mutation in cereblon (CRBN) and DNA Damage Binding Protein 1 (DDB1) genes in myeloma cells and patients and its clinical significance [abstract 3139]. ASH Annual Meeting Abstracts; 2013
  • Gandhi AK, Mendy D, Waldman M, et al. Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity. Br J Haematol 2014;164(2):233-44
  • Streetly MJ, Gyertson K, Daniel Y, et al. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol 2008;141:41-51
  • Richardson PG, Siegel D, Baz R, et al. Phase I study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood 2013;121:1961-7
  • Mikhael JR, Hayman SR, Laumann K, et al. Long term outcome of pomalidomide and dexamethasone in patients with relapsed multiple myeloma: analysis 4 years after the original cohort [abstract 2942]. ASH Annual Meeting Abstracts; 2011
  • 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
  • Lacy MQ, Allred JB, Gertz MA, et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 2011;118:2970-5
  • Lacy MQ, Kumar SK, LaPlant BR, et al. Pomalidomide plus low-dose dexamethasone (pom/dex) in relapsed myeloma: long term follow up and factors predicting outcome in 345 patients [abstract 201]. ASH Annual Meeting Abstracts; 2012
  • Hwa YL, Laumann KM, LaPlant BR, et al. Effect of immediate prior-line lenalidomide or thalidomide therapy on response to pomalidomide in multiple myeloma [abstract 1979]. ASH Annual Meeting Abstracts; 2013
  • Richardson PG, Siegel DS, Vij R, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood 2014;123(12):1826-32
  • Vij R, Hofmeister CC, Richardson PG, et al. Pomalidomide (Pom) with low-dose dexamethasone (LoDex) in patients with relapsed and refractory multiple myeloma (RRMM): outcome based on prior treatment exposure [abstract 4070]. ASH Annual Meeting Abstracts; 2012
  • Richardson PG, Jakubowiak A, Bahlis NJ, et al. Treatment outcomes with pomalidomide (Pom) in combination with low-dose dexamethasone (LoDex) in patients with relapsed and refractory multiple myeloma (RRMM) and del(17p13) and(or t(4;14) (p16;q32) cytogenetics abnormalities who have received prior therapy with lenalidomide and bortezomib [abstract 4053]. ASH Annual Meeting Abstracts; 2012
  • Vij R, Richardson PG, Siegel DS, et al. Pomalidomide plus low-dose dexamethasone (Pom + LowDex) in RRMM: analyses based on prior therapy and renal function [abstract p-170]. IMW Meeting Abstracts; 2013
  • Leleu X, Attal M, Arnulf B, et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: intergroup Francophone du Myelome 2009-02. Blood 2013;121:1968-75
  • Larocca A, Montefusco V, Bringhen S, et al. Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study. Blood 2013;122:2799-806
  • Baz R, Martin TG, Alsina M, et al. Pomalidomide (Pom) dexamethasone (D) with or without oral weekly cyclophosphamide (Cy) for lenalidomide refractory multiple myeloma (LRMM): a multicenter randomized phase II trial [abstract 3200]. ASH Annual Meeting Abstracts; 2013
  • Berenson JR, Hilger JD, Klein L, et al. Pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed/refractory multiple myeloma: results from a phase1/2 trial [abstract 3218]. ASH Annual Meeting Abstracts; 2013
  • Mark TM, Boyer A, Rossi AC, et al. Clapd (Clarithromycin, Pomalidomide, Dexamethasone) therapy in relapsed or refractory multiple myeloma [abstract 1955]. ASH Annual Meeting Abstracts; 2013
  • Mikhael JR, Roy V, Richardson PG, et al. A phase I/II trial of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma [abstract 1940]. ASH Annual Meeting Abstracts; 2013
  • Shah JJ, Stadtmauer EA, Abonour R, et al. Phase I/II dose expansion of a multi-center trial of carfilzomib and pomalidomide with dexamethasone (Car-Pom-d) in patients with relapsed/refractory multiple myeloma [abstract 690]. ASH Annual Meeting Abstracts; 2013
  • Mark TM, Allan JN, Boyer A, et al. Sequence impact of pomalidomide and carfilzomib on treatment response in relapsed multiple myeloma [abstract 1954]. ASH Annual Meeting Abstracts; 2013
  • San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomized, open-label, phase 3 trial. Lancet Oncol 2013;14:1055-66
  • Dimopoulos MA, Weisel K, Song KW, et al. Final analysis, cytogenetics, long-term treatment, and long-term survival in MM-003, a phase 3 study comparing pomalidomide + low-dose dexamethasone (Pom + LoDex) vs high-dose dexamethasone (HiDex) in relapsed/refractory multiple myeloma (RRMM) [abstract 408]. ASH Annual Meeting Abstracts; 2013
  • San Miguel JF, Weisel K, Song KW, et al. Patient outcomes by prior therapies and depth of response: analysis of MM-003, a phase 3 study comparing pomalidomide + low-dose dexamethasone (Pom + LoDex) vs high-dose dexamethasone (HiDex) in relapsed/refractory multiple myeloma (RRMM) [abstract 686]. ASH Annual Meeting Abstracts; 2013
  • Weisel K, San Miguel JF, Song KW, et al. MM-003 phase 3 study of pomalidomide in combination with low-dose dexamethasone (Pom + LoDex) vs high-dose dexamethasone (HiDex) in relapsed/refractory multiple myeloma (RRMM): Pom + LoDex is beneficial for elderly patients (>65 years of age) [abstract 3198]. ASH Annual Meeting Abstracts 2013
  • Song KW, Dimopoulos MA, Weisel K, et al. Pomalidomide (Pom) plus low-dose dexamethasone (LoDex) improves health-related quality of life (HRQoL) vs high-dose dexamethasone (HiDex) in relapsed refractory multiple myeloma (RRMM) patients enrolled in MM-003 phase 3 randomized trial [abstract 2939]. ASH Annual Meeting Abstracts; 2013
  • Siegel DS, Richardson PG, Dimopoulos MA, et al. Efficacy and safety of pomalidomide plus low-dose dexamethasone in advanced multiple myeloma: results of randomized phase 2 and 3 trials (MM-002/MM-003) [abstract 3185]. ASH Annual Meeting Abstracts 2013
  • Leleu X, Karlin L, Macro M, et al. Pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma (RRMM) with deletion (del)17p and/or translocation t(4;14) [abstract 689]. ASH Annual Meeting Abstracts; 2013
  • Madan S, Kumar S. Review: extramedullary disease in multiple myeloma. Clin Adv Hematol Oncol 2009;7:802-4
  • Varettoni M, Corso A, Pica G, et al. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol 2010;21:325-30
  • Oriol A. Multiple myeloma with extramedullary disease. Adv Ther 2011;28(Suppl 7):1-6
  • Short KD, Rajkumar SV, Larson D, et al. Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma. Leukemia 2011;25:906-8
  • Mussetti A, Dalto S, Montefusco V. Effective treatment of pomalidomide in central nervous system myelomatosis. Leuk Lymphoma 2013;54:864-6
  • Palumbo A, Rajkumar SV, Dimopoulos MA. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008;22:414-23
  • Lacy M, McCurdy A. Pomalidomide. Blood 2013;122:2305-9

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