1,966
Views
9
CrossRef citations to date
0
Altmetric
REVIEW

Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy

, , , &
Pages 496-504 | Received 04 Jun 2015, Accepted 04 Aug 2015, Published online: 27 Oct 2015

REFERENCES

  • Kyle RA, Rajkumar SV. Multiple myeloma. N Eng J Med 2004;351(18):1860–1873.
  • Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 2014;28(2):269–277.
  • Wuilleme S, Robillard N, Lodé L, Beris H, Harousseau JL, Proffitt J, et al. Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma. Leukemia 2005;19(2):275–278.
  • Cremer FW, Bila J, Buck I, Kartal M, Hose D, Ittrich C, et al. Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics. Genes Chrom Cancer 2005;44(2):194–203.
  • Fonseca R, Bergsagel PL, Drasch J, Gutierrez N, Stewart AK, Morgan G, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009;23(12):2210–2221.
  • Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007;109(8):3489–3495.
  • Chng WJ, Ketterling RP, Fonseca R. Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma. Genes Chrom Cancer 2006;45(12):1111–1120.
  • Carrasco DR, Tonon G, Huang Y, Zhang Y, Sinha R, Feng B, et al. High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell 2006;9(4):313–325.
  • Chng WJ, Kumar S, Vanwier S, Ahmann G, Price-Troska T, Henderson K, et al. Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling. Cancer Res 2007;67(7):2982–2989.
  • Avet-Loiseau H1, Li JY, Facon T, Brigaudeau C, Morineau N, et al. High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies. Cancer Res 1998;58(24):5640–5645.
  • Fonseca R, Blood EA, Oken MM, Kyle RA, Dewald GW, Bailey RJ, et al. Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients. Blood 2002;99(10):3735–3741.
  • Nishida K, Yashige H, Maekawa T, Taniwaki M, Horiike S, Misawa S, et al. Chromosome rearrangement, t(6;14) (p21.1;q32.3), in multiple myeloma. Br J Haematol 1989;71(2):295–296.
  • Kuehl WM, Bergsagel PL. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest 2012;122(10):3456–3563.
  • Avet-Loiseau H1, Garand R, Lodé L, Lodé L, Harousseau JL, Bataille R, et al. Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants. Blood 2003;101(4):1570–1571.
  • Feyler S, O'Connor SJ, Rawstron AC, Ross FM, Pratt G, Drayson MT, et al. IgM myeloma: a rare entity characterized by a CD20-CD56-CD117- immunophenotype and the t(11;14). Br J Haematol 2008;140(5):547–551.
  • Garand R, Avet-Loiseau H, Accard F, Moreau P, Harousseau JL, Bataille R. t(11;14) and t(4;14) translocations correlated with mature lymphoplasmacytoid and immature morphology, respectively, in multiple myeloma. Leukemia 2003;17(10):2032–2035.
  • Hoyer JD, Hanson CA, Fonseca R, Greipp PR, Dewald GW, Kurtin PJ. The (11;14)(q13;q32) translocation in multiple myeloma. A morphologic and immunohistochemical study. Am J Clin Pathol 2000;113(6):831–837.
  • Robillard N, Avet-Loiseau H, Garand R, Pineau D, Rapp MJ, Harousseau JL, et al. CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma. Blood 2003;102(3):1070–1071.
  • Dewald GW, Therneau T, Larson D, Fink S, Smoley S, Paternoster S, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood 2005;106(10):3553–3558.
  • Gertz MA, Lacy MQ, Dispenzieri A, Litzow MR, Henderson KJ, Van Wier SA, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005;106(8):2837–2840.
  • Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B, et al.Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011;117 (18):4696–4700.
  • Sasaki K, Lu G, Saliba RM, Bashir Q, Hosing C, Popat U, et al. Impact of t(11;14)(q13;q32) on the outcome of autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 2013;19(8):1227–1232.
  • Chesi M, Nardini E, Lim R, Smith K, Kuehl W, Bergsagel P. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood 1998;92(9):3025–34.
  • Santra M, Zhan F, Tian E, Barlogie B, Shaughnessy J Jr. 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(6):2374–6.
  • Keats JJ, Reiman T, Maxwell CA, Taylor BJ, Larratt LM, Mant MJ, et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood 2003;101(4):1520–1529.
  • Avet-Loiseau H, Facon T, Daviet A, Godon C, Rapp MJ, Harousseau JL, et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myélome. Cancer Res 1999;59(18):4546–4550.
  • Fonseca R, Oken MM, Harrington D, Bailey RJ, Van Wier SA, Henderson KJ, et al. Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 2001;15(6):981–986.
  • Fonseca R, Debes-Marun CS, Picken EB, Dewald GW, Bryant SC, Winkler JM, et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 2003;102(7):2562–2567.
  • Chang H, Sloans S, Li D, Zhuang L, Yi QL, Chen CI, et al. The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant. Br J Haematol 2004;125(1):64–68.
  • Jaksic W, Trudel S, Chang H, Trieu Y, Qi X, Mikhael J, et al. Clinical outcomes in t(4;14) multiple myeloma: a chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance. J Clin Oncol 2005;23(28):7069–7073.
  • Fonseca R, Bailey RJ, Ahmann GJ, Rajkumar SV, Hoyer JD, Lust JA, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood 2002;100(4):1417–1424.
  • Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, et al. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell 2004;5(2):191–199.
  • Jenner MW, Leone PE, Walker BA, Ross FM, Johnson DC, Gonzalez D, et al. Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. Blood 2007;110(9):3291–3300.
  • Ross FM, Chiecchio L, Dagrada GP, Protheroe RK, Stockley DM, Harrison CJ, et al. The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease en monoclonal gammopathies of undetermined significance. Haematologica 2010;95(7):1221–1225.
  • Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2(3):175–187.
  • Bergsagel PL, Kuehl WM. Chromosome translocations in multiple myeloma. Oncogene 2001;20(40):5611–5622.
  • Sawyer JR. The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet 2011;204(1):3–12.
  • Fonseca R, Oken MM, Harrington D, Bailey RJ, Van Wier SA, Henderson KJ, et al. Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 2001;15(6):981–986.
  • Avet-Louseau H, Daviet A, Sauner S, Bataille R. Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13. Br J Haematol 2000;111(4):1116–1117.
  • Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003;101(11):4569–4575.
  • Chiecchio L, Protheroe RK, Ibrahim AH, Cheung KL, Rudduck C, Dagrada GP, et al. Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia 2006;20(9):1610–1617.
  • Drach J, Ackermann J, Fritz E, Krömer E, Schuster R, Gisslinger H, et al. Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy. Blood 1998;92(3):802–809.
  • Rother K, Li Y, Tschöp K, Kirschner R, Müller GA, Mössner J, et al. Expression of cyclin-dependent kinase subunit 1 (Cks1) is regulated during the cell cycle by a CDE/CHR tandem element and is downregulated by p53 but not by p63 or p73. Cell Cycle 2007;6(7):853–862.
  • Chang H, Qi C, Yi QL, Reece D, Stewart AK. p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood 2005;105(1):358–360.
  • Chang H, Sloan S, Li D, Keith Stewart A. Multiple myeloma involving central nervous system: high frequency of chromosome 17p13.1 (p53) deletions. Br J Haematol 2004;127(3):280–284.
  • Tiedemann RE, Gonzalez-Paz N, Kyle RA, Santana-Davila R, Price-Troska T, Van Wier SA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 2008;22:1044–1052.
  • Xiong W, Wu X, Starnes S, Johnson SK, Haessler J, Wang S, et al. An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma. Blood 2008;112(10):4235–4246.
  • Cremer FW, Bila J, Buck I, Kartal M, Hose D, Ittrich C, et al. Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics. Genes Chrom Cancer 2005;44(2):194–203.
  • Sawyer JR, Tricot G, Lukacs JL, Binz RL, Tian E, Barlogie B, et al. Genomic instability in multiple myeloma: evidence for jumping segmental duplications of chromosome arm 1q. Genes Chrom Cancer 2005;42(1):95–106.
  • Qazilbash MH, Saliba RM, Ahmed B, Parikh G, Mendoza F, Ashraf N, et al. Deletion of the short arm of chromosome 1(del1p) is a strong predictor of poor outcome in myeloma patients undergoing an autotransplant. Biol Blood Marrow Transplant 2007;13(9):1066–1072.
  • Chang H, Ning Y, Qi X, Yeung J, Xu W. Chromosome 1p21 deletion is a novel prognostic marker in patients with multiple myeloma. Br J Haematol 2007;139(1):51–54.
  • Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, Sawyer JR, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood 2006;108(5):1724–1732.
  • Chang H, Qi X, Jiang A, Xu W, Young T, Reece D. 1p21 deletions are strongly associated with 1q21 gains and are an independent adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma. Bone Marrow Transp 2010;45(1):117–121.
  • Stella F, Pedrazzini E, Rodríguez A, Baialardo E, Kusminsky G, Arbelbide J, et al. New recurrent chromosome alterations in patients with multiple myeloma and plasma cell leukemia. Cytogenet Genome Res 2011;134(4):249–259.
  • Walker BA, Leone PE, Chiecchio L, Dickens NJ, Jenner MW, Boyd KD, et al. A compendium of myeloma associated chromosomal copy number abnormalities and their prognostic value. Blood 2010;116 (15): e56–e65.
  • Stella F, Pedrazzini E, Baialardo E, Fantl DB, Schutz N, Slavutsky I. Quantitative analysis of CKS1B mRNA expression and copy number gain in patients with plasma cell disorders. Blood Cells Mol Dis 2014;53(3):110–117.
  • Chang H, Qi X, Trieu Y, Xu W, Reader JC, Ning Y, et al. Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantation. Br J Haematol 2006;135(4):486–491.
  • Fonseca R, Van Wier SA, Chng WJ, Ketterling R, Lacy MQ, Dispenzieri A, et al. Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma. Leukemia 2006;20(11):2034–2040.
  • Sawyer JR, Tian E, Thomas E, Koller M, Stangeby C, Sammartino G, et al. Evidence for a novel mechanism for gene amplification in multiple myeloma:1q12 pericentromeric heterochromatin mediates breakage-fusion-bridge cycles of a 1q12 approximately 23 amplicon. Br J Haematol 2009;147(4):484–494.
  • Chng WJ, Glebov O, Bergsagel PL, Kuehl WM. Genetic events in the pathogenesis of multiple myeloma. Best Pract Res Clin Haematol 2007;20(4):571–596.
  • Nemec P, Zemanova Z, Greslikova H, Michalova K, Filkova H, Tajtlova J, et al. Gain of 1q21 is an unfavorable genetic prognostic factor for multiple myeloma patients treated with high-dose chemotherapy. Biol Blood Marrow Transplant 2010;16(4):548–554.
  • Klein U, Jauch, A, Hielscher T, Hillengass J, Raab MS, Seckinger A, 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):2136–2144.
  • Pines J. Cell cycle: reaching for a role for the Cks proteins. Curr Biol 1996;6(11):1399–1402.
  • Reed SI. Ratchets and clocks: the cell cycle, ubiquitylation and protein turnover. Nature Rev Mol Cell Biol 2003;4(11):855–864.
  • Cardozo T, Pagano M. The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 2004;5(9):739–751.
  • Decaux O, Lodé L, Mangrangeas F, Charbonnel C, Gouraud W, Jézéquel P, 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):4798–4805.
  • Zhan F, Colla S, Wu X, Chen B, Stewart JP, Kuehl WM, et al. Cks1b. Overexpressed in aggressive disease, regulates multiple myeloma growth and survival through skp2- and p27kip1-dependent and -independent mechanisms. Blood 2007;109(11):4995–5001.
  • Kassambara A, Hose D, Moreaux J, Walker BA, Protopopov A, Reme T, et al. Genes with a spike expression are clustered in chromosome (sub)bands and spike (sub)bands have a powerful prognostic value in patients with multiple myeloma. Haematologica 2012:97(4):622–630.
  • Mosca L, Musto P, Todoerti K, Barbieri M, Agnelli L, Fabris S, et al. Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles. Am J Hematol 2013;88(1):16–23.
  • Shaughnessy J. Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma. Hematology 2005;10(Suppl. 1):117–126.
  • Grzasko N, Hus M, Pluta A, Jurczyszyn A, Walter-Croneck A, Morawska M, et al. Additional genetic abnormalities significantly worsen poor prognosis associated with 1q21 amplification in multiple myeloma patients. Hematol Oncol 2013;31(1):41–48.
  • Gutierrez NC, Garcia JL, Hernandez JM, Lumbreras E, Castellanos M, Rasillo A, et al. Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma. Blood 2004;104(9):2661–2666.
  • Leone PE, Walker BA, Jenner MW, Chiecchio L, Dagrada G, Protheroe RK, et al. Deletions of CDKN2C in multiple myeloma: biological and clinical Implications. Clin Cancer Res 2008;14(19):6033–6041.
  • Kulkarni MS, Daggett JL, Bender TP, Kuehl WM, Bergsagel PL, Williams ME. Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis. Leukemia 2002;16(1):127–134.
  • Dib A, Peterson TR, Raducha-Grace L, Zingone A, Zhan F, Hanamura I, et al. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs. increased expression. Cell Div 2006;1:23.
  • Schrantz N, Beney GE, Auffredou MT, Bourgeade MF, Leca G, Vazquez A. The expression of p18INK4 and p27kip1 cyclin-dependent kinase inhibitors is regulated differently during human B cell differentiation. J Immunol 2000;165(8):4346–4352.
  • Chng WJ, Gertz MA, Chung T-H, Van Wier S, Keats JJ, Baker A, et al. Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: Identification of 1p31–32 deletion as a prognostic factor in myeloma. Leukemia 2010;24(4):833–842.
  • Hebraud B, Leleu X, Lauwers-Cances V, Roussel M, Caillot D, Marit G, et al. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients. Leukemia 2014;28(3):675–679.
  • Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol 2005;23(26):6333–6338.
  • Avet-Loiseau H, Gerson F, Magrangeas F, Minvielle S, Harousseau JL, Bataille R et al. Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors. Blood 2001;98(10):3082–3086.
  • Gabrea A, Martelli ML, Qi Y, Roschke A, Barlogie B, Shaughnessy JD Jr et al. Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors. Genes Chrom Cancer 2008;47(7):573–590.
  • Chng WJ, Huang GF, Chung TH, Ng SB, Gonzalez-Paz N, Troska-Price T, et al. Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma. Leukemia 2011;25(6):1026–1035.
  • Chesi M, Robbiani DF, Sebag M, Chng WJ, Affer M, Tiedemann R, et al. AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies. Cancer Cell 2008;13(2):167–180.
  • Jiang N, Qi C, Yu L, Ning Y, An G, Qiu L, et al. Analysis of chromosome 12p deletion in plasma cell dyscrasias. Leuk Res 2012;36(1):32–36.
  • Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, et al. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 2012;97(3):442–450.
  • Sonneveld P, Schmidt-Wolf IGH, van der Holt B, El Jarari L, Bertsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol 2012;30(24):2946–2955.
  • Cavo M, Tacchetti P, Patriarca F, Pantani L, Galli M, Di Raimondo F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and as consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomized phase 3 study. Lancet 2010;376(9758):2075–2085.
  • Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood 2012;120(1):9–19.
  • Rosinol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012;120(8):1589–1596.
  • Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood 2011;118(5):1231–1238.
  • San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus Melphalan and Prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359(9):906–917.
  • Mateos MV, Oriol A, Martinez-Lopez J, Gutiérrez N, Teruel AI, de Paz R, et al. Botezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus boirtezomib and prednisone in elderly patients with untreated multiple myeloma: a randomized trial. Lancet Oncol 2010, 11(10):934–941.
  • Mateos MV, Oriol A, Martinez-Lopez J, Gutiérrez N, Teruel AI, López de la Guía A, et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patiens included in the GEM2005MAS65 trial. Blood 2012;120(13):2581–2588.
  • Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 2010;28(34):5101–5109.
  • McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366(19):1770–1781.
  • Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366(19):1782–1791.
  • Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 2014; 371(10):906–917.
  • Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012;366(19): 1759–69.
  • Sonneveld P, Goldschmidt H, Rosiñol L, Bladé J, Lahuerta JJ, Cavo M, et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol 2013;31(26):3279–3287.
  • Moreau P, Cavo M, Sonneveld P, Rosinol L, Attal M, Pezzi A, 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):2173–2180.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.