Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy

References

• Mahindra A, Hideshima T, Anderson KC. Multiple myeloma: biology of the disease. Blood Rev 2010;24(Suppl 1):S5-11
   PubMedGoogle Scholar
• Boyle EM, Davies FE, Leleu X, Morgan GJ. Understanding the multiple biological aspects leading to myeloma. Haematologica 2014;9(4):605-12
   Google Scholar
• Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer 2012;12(5):335-48
   PubMed Web of Science ®Google Scholar
• Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111(5):2516-20
   PubMed Web of Science ®Google Scholar
• Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 2014;28(5):1122-8
   PubMed Web of Science ®Google Scholar
• Mateos MV, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 2010;28(13):2259-66
   PubMed Web of Science ®Google Scholar
• Lendvai N, Hilden P, Devlin S, et al. A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed or refractory multiple myeloma. Blood 2014;124(6):899-906
   PubMed Web of Science ®Google Scholar
• Richardson PG, Baz R, Wang M, et al. Phase 1 study of twice-weekly dosing of investigational oral proteasome inhibitor ixazomib in patients with relapsed and/or refractory multiple myeloma. Blood 2014;124(11):1038-46
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Kuroda J, Nagoshi H, Shimura Y, Taniwaki M. Elotuzumab and daratumumab: emerging new monoclonal antibodies for multiple myeloma. Expert Rev Anticancer Ther 2013;13(9):1081-8
   PubMed Web of Science ®Google Scholar
• 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(16):1953-9
   PubMed Web of Science ®Google Scholar
• Bolli N, Avet-Loiseau H, Wedge DC, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun 2014;5:2997
   PubMed Web of Science ®Google Scholar
• Walker BA, Wardell CP, Melchor L, et al. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia 2014;28(2):384-90
   PubMed Web of Science ®Google Scholar
• Walker BA, Wardell CP, Melchor L, et al. Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma. Blood 2012;120(5):1077-86
   PubMed Web of Science ®Google Scholar
• Richardson PG, Schlossman RL, 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007;357(21):2133-42
   PubMed Web of Science ®Google Scholar
• Reece D, Song KW, Fu T, et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood 2009;114(3):522-5
   PubMed Web of Science ®Google Scholar
• Avet-Loiseau H, Soulier J, Fermand JP, et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia 2010;24(3):623-8
   PubMed Web of Science ®Google Scholar
• Chang H, Jiang A, Qi C, et al. Impact of genomic aberrations including chromosome 1 abnormalities on the outcome of patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Leuk Lymphoma 2010;51(11):2084-91
   PubMed Web of Science ®Google Scholar
• Klein U, Jauch A, Hielscher T, et al. Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer 2011;117(10):2136-44
   PubMed Web of Science ®Google Scholar
• Kim K, Kim SJ, Voelter V, et al. Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea-experience from 110 patients. Ann Hematol 2014;93(1):113-21
   Google Scholar
• Dimopoulos MA, Kastritis E, Christoulas D, et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia 2010;24(10):1769-78
   PubMed Web of Science ®Google Scholar
• Huang SY, Lin CW, Lin HH, et al. Expression of cereblon protein assessed by immunohistochemical staining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, but not bortezomib-based treatment, in patients with multiple myeloma. Ann Hematol 2014;93(8):1371-80
   PubMed Web of Science ®Google Scholar
• Chen MH, Qi CX, Saha MN, Chang H. p53 nuclear expression correlates with hemizygous TP53 deletion and predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with lenalidomide. Am J Clin Pathol 2012;137(2):208-12
   PubMed Web of Science ®Google Scholar
• Alegre A, Aguado B, Giraldo P, et al. Lenalidomide is effective as salvage therapy in refractory or relapsed multiple myeloma: analysis of the Spanish Compassionate Use Registry in advanced patients. Int J Hematol 2011;93(3):351-60
   PubMed Web of Science ®Google Scholar
• Kleber M, Ihorst G, Udi J, et al. Prognostic risk factor evaluation in patients with relapsed or refractory multiple myeloma receiving lenalidomide treatment: analysis of renal function by eGFR and of additional comorbidities by comorbidity appraisal. Clin Lymphoma Myeloma Leuk 2012;12(1):38-48
   PubMed Web of Science ®Google Scholar
• Katodritou E, Vadikolia C, Lalagianni C, et al. “Real-world” data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group. Ann Hematol 2014;93(1):129-39
   PubMed Web of Science ®Google Scholar
• Stadtmauer EA, Weber DM, Niesvizky R, et al. Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma. Eur J Haematol 2009;82(6):426-32
   PubMed Web of Science ®Google Scholar
• Guglielmelli T, Bringhen S, Rrodhe S, et al. Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients. Eur J Cancer 2011;47(6):814-18
   Google Scholar
• Wang M, Dimopoulos MA, Chen C, et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 2008;112(12):4445-51
   PubMed Web of Science ®Google Scholar
• Jacobus SJ, Kumar S, Uno H, et al. Impact of high-risk classification by FISH: an eastern cooperative oncology group (ECOG) study E4A03. Br J Haematol 2011;155(3):340-8
   PubMed Web of Science ®Google Scholar
• Kumar SK, Uno H, Jacobus SJ, et al. Impact of gene expression profiling-based risk stratification in patients with myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood 2011;118(16):4359-62
   Google Scholar
• Kapoor P, Kumar S, Fonseca R, et al. Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood 2009;114(3):518-21
   PubMed Web of Science ®Google Scholar
• Srivastava G, Rana V, Lacy MQ, et al. Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma. Leukemia 2013;27(10):2062-6
   Google Scholar
• Heintel D, Rocci A, Ludwig H, et al. High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone. Br J Haematol 2013;161(5):695-700
   PubMed Web of Science ®Google Scholar
• 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 randomised controlled trial. Lancet Oncol 2010;11(1):29-37
   PubMed Web of Science ®Google Scholar
• Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev 2010;24(Suppl 1):S13-19
   PubMed Web of Science ®Google Scholar
• Zhu YX, Kortuem KM, Stewart AK. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma 2013;54(4):683-7
   PubMed Web of Science ®Google Scholar
• Chang X, Zhu Y, Shi C, Stewart AK. Mechanism of immunomodulatory drugs’ action in the treatment of multiple myeloma. Acta Biochim Biophys Sin (Shanghai) 2014;46(3):240-53
   Google Scholar
• LeBlanc R, Hideshima T, Catley LP, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood 2004;103(5):1787-90
   PubMed Web of Science ®Google Scholar
• Schafer PH, Gandhi AK, Loveland MA, et al. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther 2003;305(3):1222-32
   PubMed Web of Science ®Google Scholar
• 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(17):3227-37
   PubMed Web of Science ®Google Scholar
• Marriott JB, Clarke IA, Dredge K, et al. Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4(+) and CD8(+) T cells. Clin Exp Immunol 2002;130(1):75-84
   PubMed Web of Science ®Google Scholar
• Dredge K, Marriott JB, Todryk SM, et al. Protective antitumor immunity induced by a costimulatory thalidomide analog in conjunction with whole tumor cell vaccination is mediated by increased Th1-type immunity. J Immunol 2002;168(10):4914-19
   PubMed Web of Science ®Google Scholar
• Henry JY, Labarthe MC, Meyer B, et al. Enhanced cross-priming of naive CD8+ T cells by dendritic cells treated by the IMiDsg of naive CD8+ T/pubmed/233lenalidomide and pomalidomide. Immunology 2013;139(3):377-85
   PubMed Web of Science ®Google Scholar
• Reddy N, Hernandez-Ilizaliturri FJ, Deeb G, et al. Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol 2008;140(1):36-45
   PubMed Web of Science ®Google Scholar
• Muthu Raja KR, Kovarova L, Stossova J, Hajek R. Flow cytometric phenotyping and analysis of T regulatory cells in multiple myeloma patients. Klin Onkol 2011;24(Suppl):S30-3
   Google Scholar
• 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(7):1033-45
   PubMed Web of Science ®Google Scholar
• Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res 2008;14(14):4650-7
   PubMed Web of Science ®Google Scholar
• Benson DMJr, Bakan CE, Mishra A, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood 2010;116(13):2286-94
   PubMed Web of Science ®Google Scholar
• Chang DH, Liu N, Klimek V, et al. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood 2006;108(2):618-21
   PubMed Web of Science ®Google Scholar
• Görgün GT, Whitehill G, Anderson JL, et al. Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. Blood 2013;121(15):2975-87
   PubMed Web of Science ®Google Scholar
• Abdi J, Chen G, Chang H. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget 2013;4(12):2186-207
   PubMed Web of Science ®Google Scholar
• Manier S, Sacco A, Leleu X, et al. Bone marrow microenvironment in multiple myeloma progression. J Biomed Biotechnol 2012;2012:157496
   PubMed Web of Science ®Google Scholar
• Podar K, Chauhan D, Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia 2009;23(1):10-24
   PubMed Web of Science ®Google Scholar
• Karadag A, Oyajobi BO, Apperley JF, et al. Human myeloma cells promote the production of interleukin 6 by primary human osteoblasts. Br J Haematol 2000;108(2):383-90
   Google Scholar
• Thomas X, Anglaret B, Magaud JP, et al. Interdependence between cytokines and cell adhesion molecules to induce interleukin-6 production by stromal cells in myeloma. Leuk Lymphoma 1998;32(1-2):107-19
   PubMed Web of Science ®Google Scholar
• Klein B, Tarte K, Jourdan M, et al. Survival and proliferation factors of normal and malignant plasma cells. Int J Hematol 2003;78(2):106-13
   PubMed Web of Science ®Google Scholar
• Hideshima T, Chauhan D, Schlossman R, et al. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene 2001;20(33):4519-27
   PubMed Web of Science ®Google Scholar
• Roccaro AM, Sacco A, Maiso P, et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest 2013;123(4):1542-55
   PubMed Web of Science ®Google Scholar
• Wang J, Hendrix A, Hernot S, et al. Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood 2014;124(4):555-66
   PubMed Web of Science ®Google Scholar
• Terpos E, Efstathiou E, Christoulas D, et al. RANKL inhibition: clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases. Expert Opin Biol Ther 2009;9(4):465-79
   PubMed Web of Science ®Google Scholar
• Abe M. Targeting the interplay between myeloma cells and the bone marrow microenvironment in myeloma. Int J Hematol 2011;94(4):334-43
   PubMed Web of Science ®Google Scholar
• Buckle CH, De Leenheer E, Lawson MA, et al. Soluble rank ligand produced by myeloma cells causes generalised bone loss in multiple myeloma. PLoS One 2012;7(8):e41127
   PubMed Web of Science ®Google Scholar
• Dredge K, Marriott JB, Macdonald CD, et al. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer 2002;87(10):1166-72
   PubMed Web of Science ®Google Scholar
• De Luisi A, Ferrucci A, Coluccia AM, et al. Lenalidomide restrains motility and overangiogenic potential of bone marrow endothelial cells in patients with active multiple myeloma. Clin Cancer Res 2011;17(7):1935-46
   PubMed Web of Science ®Google Scholar
• Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia 2008;22(10):1925-32
   PubMed Web of Science ®Google Scholar
• 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(12):4525-30
   PubMed Web of Science ®Google Scholar
• Tai YT, Li XF, Catley L, et al. Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications. Cancer Res 2005;65(24):11712-20
   PubMed Web of Science ®Google Scholar
• Gandhi AK, Kang J, Capone L, et al. Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 2010;10(2):155-67
   PubMed Web of Science ®Google Scholar
• Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, et al. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res 2009;69(18):7347-56
   PubMed Web of Science ®Google Scholar
• Annunziata CM, Davis RE, Demchenko Y, et al. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 2007;12(2):115-30
   PubMed Web of Science ®Google Scholar
• Li S, Pal R, Monaghan SA, et al. IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM. Blood 2011;117(19):5157-65
   PubMed Web of Science ®Google Scholar
• Shaffer AL, Emre NC, Lamy L, et al. IRF4 addiction in multiple myeloma. Nature 2008;454(7201):226-31
   PubMed Web of Science ®Google Scholar
• Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 2011;118(18):4771-9
   PubMed Web of Science ®Google Scholar
• 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(11):2326-35
   PubMed Web of Science ®Google Scholar
• Lu G, Middleton RE, Sun H, et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 2014;343(6168):305-9
   PubMed Web of Science ®Google Scholar
• Krönke J, Udeshi ND, Narla A, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 2014;343(6168):301-5
   PubMed Web of Science ®Google Scholar
• Gandhi AK, Kang J, Havens CG, et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br J Haematol 2014;164(6):811-21
   PubMed Web of Science ®Google Scholar
• Zhu YX, Braggio E, Shi CX, et al. Identification of cereblon binding proteins and relationship with response and survival following pomalidomide and dexamethasone in multiple myeloma. Blood 2014;124(4):536-45
   PubMed Web of Science ®Google Scholar
• Christiansen A, Dyrskjøt L. The functional role of the novel biomarker karyopherin α2 (KPNA2) in cancer. Cancer Lett 2013;331(1):18-23
   PubMed Web of Science ®Google Scholar
• Munshi NC, Anderson KC, Bergsagel PL, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011;117(18):4696-700
   PubMed Web of Science ®Google Scholar
• Chesi M, Bergsagel PL. Molecular pathogenesis of multiple myeloma: basic and clinical updates. Int J Hematol 2013;97(3):313-23
   PubMed Web of Science ®Google Scholar
• Avet-Loiseau H, Hulin C, Campion L, et al. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myélome experience. J Clin Oncol 2013;31(22):2806-9
   PubMed Web of Science ®Google Scholar
• Paiva B, Gutiérrez NC, Rosiñol L, et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood 2012;119(3):687-91
   PubMed Web of Science ®Google Scholar
• Fonseca R, Oken MM, Greipp PR; Eastern Cooperative Oncology Group Myeloma Group. The t(4;14)(p16.3;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance. Blood 2001;98(4):1271-2
   Google Scholar
• Dewald GW, Therneau T, Larson D, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood 2005;106(10):3553-8
   PubMed Web of Science ®Google Scholar
• Kiyota M, Kobayashi T, Fuchida S, et al. Monosomy 13 in metaphase spreads is a predictor of poor long-term outcome after bortezomib plus dexamethasone treatment for relapsed/refractory multiple myeloma. Int J Hematol 2012;95(5):516-26
   Google Scholar
• Lodé L, Eveillard M, Trichet V, et al. Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma. Haematologica 2010;95(11):1973-6
   PubMed Web of Science ®Google Scholar
• Boyd KD, Ross FM, Tapper WJ, et al. The clinical impact and molecular biology of del(17p) in multiple myeloma treated with conventional or thalidomide-based therapy. Genes Chromosomes Cancer 2011;50(10):765-74
   PubMed Web of Science ®Google Scholar
• Kang S, Dong S, Gu TL, et al. FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway. Cancer Cell 2007;12(3):201-14
   PubMed Web of Science ®Google Scholar
• Ronchetti D, Greco A, Compasso S, et al. Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations. Oncogene 2001;20(27):3553-62
   Google Scholar
• Shimura Y, Kuroda J, Ri M, et al. RSK2(Ser227) at N-terminal kinase domain is a potential therapeutic target for multiple myeloma. Mol Cancer Ther 2012;11(12):2600-9
   Google Scholar
• Zhu YX, Yin H, Bruins L, et al. RNA interference screening identifies lenalidomide sensitizers in multiple myeloma, including RSK2. Blood 2015;125(3):483-91
   Google Scholar
• Lopez-Girona A, Heintel D, Zhang LH, et al. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol 2011;154(3):325-36
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Chang H, Yeung J, Qi C, Xu W. Aberrant nuclear p53 protein expression detected by immunohistochemistry is associated with hemizygous P53 deletion and poor survival for multiple myeloma. Br J Haematol 2007;138(3):324-9
   Google Scholar
• Shaughnessy JDJr, Zhan F, Burington BE, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood 2007;109(6):2276-84
   PubMed Web of Science ®Google Scholar
• Decaux O, Lodé L, Magrangeas F, et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome. J Clin Oncol 2008;26(29):4798-805
   PubMed Web of Science ®Google Scholar
• Burington B, Barlogie B, Zhan F, et al. Tumor cell gene expression changes following short-term in vivo exposure to single agent chemotherapeutics are related to survival in multiple myeloma. Clin Cancer Res 2008;14(15):4821-9
   Google Scholar
• Muthu Raja KR, Kovarova L, Hajek R. Induction by lenalidomide and dexamethasone combination increases regulatory cells of patients with previously untreated multiple myeloma. Leuk Lymphoma 2012;53(7):1406-8
   PubMed Web of Science ®Google Scholar
• Gupta R, Ganeshan P, Hakim M, et al. Significantly reduced regulatory T cell population in patients with untreated multiple myeloma. Leuk Res 2011;35(7):874-8
   PubMed Web of Science ®Google Scholar
• Busch A, Zeh D, Janzen V, et al. Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients. Clin Exp Immunol 2014;177(2):439-53
   Google Scholar
• Chan AC, Neeson P, Leeansyah E, et al. Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy. Clin Exp Immunol 2014;175(1):49-58
   Google Scholar
• Cibeira MT, Rozman M, Segarra M, et al. Bone marrow angiogenesis and angiogenic factors in multiple myeloma treated with novel agents. Cytokine 2008;41(3):244-53
   Google Scholar
• Harada T, Ozaki S, Oda A, et al. Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma. Int J Hematol 2013;97(6):743-8
   Google Scholar
• Zamarin D, Devlin SM, Arcila ME, et al. Polyclonal immune activation and marrow plasmacytosis in multiple myeloma patients receiving long-term lenalidomide therapy: incidence and prognostic significance. Leukemia 2013;27(12):2422-4
   Google Scholar
• Mark T, Jayabalan D, Coleman M, et al. Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma. Br J Haematol 2008;143(5):654-60
   PubMedGoogle Scholar
• Alejandre ME, Madalena LB, Pavlovsky MA, et al. Oligoclonal bands and immunoglobulin isotype switch during monitoring of patients with multiple myeloma and autologous hematopoietic cell transplantation: a 16-year experience. Clin Chem Lab Med 2010;48(5):727-31
   Google Scholar
• Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23(15):3412-20
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Kuroda J, Fuchida SI, et al. Impact of early use of lenalidomide and low-dose dexamethasone on clinical outcomes in patients with relapsed/refractory multiple myeloma. Int J Hematol 2015;101(1):37-45
   Google Scholar
• Kleber M, Ihorst G, Gross B, et al. Validation of the Freiburg Comorbidity Index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome. Clin Lymphoma Myeloma Leuk 2013;13(5):541-51
   PubMed Web of Science ®Google Scholar
• Tan D, Kim K, Kim JS, et al. The impact of upfront versus sequential use of bortezomib among patients with newly diagnosed multiple myeloma (MM): a joint analysis of the Singapore MM Study Group and the Korean MM Working Party for the Asian myeloma network. Leuk Res 2013;37(9):1070-6
   Google Scholar
• Maltezas D, Dimopoulos MA, Katodritou I, et al. Re-evaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents. Hematol Oncol 2013;31(2):356-62
   Google Scholar
• Moreau P, Cavo M, Sonneveld P, et al. Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death. J Clin Oncol 2014;32(20):2173-80
   PubMed Web of Science ®Google Scholar
• Keats JJ, Chesi M, Egan JB, et al. Clonal competition with alternating dominance in multiple myeloma. Blood 2012;120(5):1067-76
   PubMed Web of Science ®Google Scholar
• Egan JB, Shi CX, Tembe W, et al. Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood 2012;120(5):1060-6
   PubMed Web of Science ®Google Scholar
• Mateos MV, Martinez-Lopez J, Hernandez M, et al. Comparison of sequential vs alternating administration of bortezomib, melphalan, prednisone (VMP) and lenalidomide plus dexamethasone (Rd) in elderly pts with newly diagnosed multiple myeloma (MM) patients: GEM2010MAS65 trial. Blood 2014;124(21):178
   Google Scholar
• Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366(19):1782-91
   PubMed Web of Science ®Google Scholar
• McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366(19):1770-81
   PubMed Web of Science ®Google Scholar
• Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 2013;369(5):438-47
   PubMed Web of Science ®Google Scholar
• Khagi Y, Mark TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther 2014;7:1095-100
   PubMed Web of Science ®Google Scholar