Novel agents and new therapeutic approaches for treatment of multiple myeloma
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  • 英文篇名:Novel agents and new therapeutic approaches for treatment of multiple myeloma
  • 作者:Roberto ; Ria ; Antonia ; Reale ; Angelo ; Vacca
  • 英文作者:Roberto Ria;Antonia Reale;Angelo Vacca;Section of Internal Medicine, Department of Biomedical Sciences and Human On-cology,University of Bari Medical School,I-70124 Bari,Italy;
  • 英文关键词:Immunomodulators;;Multiple myeloma;;New drugs;;Proteasome inhibitors;;Target therapy
  • 中文刊名:SJFF
  • 英文刊名:世界方法学杂志(英文版)
  • 机构:Section of Internal Medicine, Department of Biomedical Sciences and Human On-cology,University of Bari Medical School,I-70124 Bari,Italy;
  • 出版日期:2014-06-26
  • 出版单位:World Journal of Methodology
  • 年:2014
  • 期:v.4
  • 基金:Supported by Associazione Italiana per la Ricerca sul Cancro(Italian Association for Cancer Research-AIRC),Investigator Grant and the 5 per thousand Molecular Clinical Oncology Special Program,No.9965;; Milan,to AV,the European Commission's Seventh Framework programme(EU-FPT7)under grant agreement(OVER-My R)to AV,No.278706;; EU FPT7(2007-2013)under grant agreement to DR,No.278570;; grants from MIUR PRIN to RR,No.2009WCNS5C_004;; grants from MIUR PRIN to AV,No.2010NECHBX
  • 语种:英文;
  • 页:SJFF201402003
  • 页数:18
  • CN:02
  • 分类号:34-51
摘要
This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein(immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents(bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality respons-es with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.
        This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein(immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents(bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality respons-es with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.
引文
1 Palumbo A,Anderson K.Multiple myeloma.N Engl J Med2011;364:1046-1060[PMID:21410373 DOI:10.1056/NEJMra1011442]
    2 Chanan-Khan AA,Giralt S.Importance of achieving a complete response in multiple myeloma,and the impact of novel agents.J Clin Oncol 2010;28:2612-2624[PMID:20385994DOI:10.1200/JCO.2009.25.4250]
    3 Borrello I.Can we change the disease biology of multiple myelomaLeuk Res 2012;36 Suppl 1:S3-12[PMID:23176722DOI:10.1016/S0145-2126(12)70003-6]
    4 Manier S,Sacco A,Leleu X,Ghobrial IM,Roccaro AM.Bone marrow microenvironment in multiple myeloma progression.J Biomed Biotechnol 2012;2012:157496[PMID:23093834DOI:10.1155/2012/157496]
    5 Gertz MA,Ansell SM,Dingli D,Dispenzieri A,Buadi FK,Elliott MA,Gastineau DA,Hayman SR,Hogan WJ,Inwards DJ,Johnston PB,Kumar S,Lacy MQ,Leung N,Micallef IN,Porrata LF,Schafer BA,Wolf RC,Litzow MR.Autologousstem cell transplant in 716 patients with multiple myeloma:low treatment-related mortality,feasibility of outpatient transplant,and effect of a multidisciplinary quality initiative.Mayo Clin Proc 2008;83:1131-1138[PMID:18828972 DOI:10 .4065/83.10.1131]
    6 Moreau P,Rajkumar SV.“Should all eligible patients with multiple myeloma receive autologous stem-cell transplant as part of initial treatment”.Leuk Res 2012;36:677-681[PMID:22430045 DOI:10.1016/j.leukres.2012.02.023]
    7 Cavo M,Tosi P,Zamagni E,Cellini C,Tacchetti P,Patriarca F,Di Raimondo F,Volpe E,Ronconi S,Cangini D,Narni F,Carubelli A,Masini L,Catalano L,Fiacchini M,de Vivo A,Gozzetti A,Lazzaro A,Tura S,Baccarani M.Prospective,randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma:Bologna 96 clinical study.J Clin Oncol 2007;25:2434-2441[PMID:17485707]
    8 Palumbo A,Niesvizky R.Sustained disease control in transplant-ineligible patients:the role of continuous therapy.Leuk Res 2012;36 Suppl 1:S19-S26[PMID:23176720 DOI:10.1016/S0145-2126(12)70005-X]
    9 Kumar SK,Rajkumar SV,Dispenzieri A,Lacy MQ,Hayman SR,Buadi FK,Zeldenrust SR,Dingli D,Russell SJ,Lust JA,Greipp PR,Kyle RA,Gertz MA.Improved survival in multiple myeloma and the impact of novel therapies.Blood 2008;111 :2516-2520[PMID:17975015]
    10 Dispenzieri A,Jacobus S,Vesole DH,Callandar N,Fonseca R,Greipp PR.Primary therapy with single agent bortezomib as induction,maintenance and re-induction in patients with high-risk myeloma:results of the ECOG E2A02 trial.Leukemia 2010;24:1406-1411[PMID:20535147 DOI:10.1038/leu.2010.129]
    11 Harousseau JL,Attal M,Avet-Loiseau H,Marit G,Caillot D,Mohty M,Lenain P,Hulin C,Facon T,Casassus P,Michallet M,Maisonneuve H,Benboubker L,Maloisel F,Petillon MO,Webb I,Mathiot C,Moreau P.Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stemcell transplantation in newly diagnosed multiple myeloma:results of the IFM 2005-01 phase III trial.J Clin Oncol 2010;28:4621-4629[PMID:20823406 DOI:10.1200/JCO.2009.27.9158]
    12 Cavo M,Tacchetti P,Patriarca F,Petrucci MT,Pantani L,Galli M,Di Raimondo F,Crippa C,Zamagni E,Palumbo A,Offidani M,Corradini P,Narni F,Spadano A,Pescosta N,Deliliers GL,Ledda A,Cellini C,Caravita T,Tosi P,Baccarani M.Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before,and consolidation therapy after,double autologous stem-cell transplantation in newly diagnosed multiple myeloma:a randomised phase 3 study.Lancet 2010;376:2075-2085[PMID:21146205 DOI:10.1016/S0140-6736(10)61424-9]
    13 Moreau P,Avet-Loiseau H,Facon T,Attal M,Tiab M,Hulin C,Doyen C,Garderet L,Randriamalala E,Araujo C,Lepeu G,Marit G,Caillot D,Escoffre M,Lioure B,Benboubker L,PégouriéB,Kolb B,Stoppa AM,Fuzibet JG,Decaux O,Dib M,Berthou C,Chaleteix C,Sebban C,TraulléC,Fontan J,Wetterwald M,Lenain P,Mathiot C,Harousseau JL.Bortezomib plus dexamethasone versus reduced-dose bortezomib,thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma.Blood 2011;118:5752-5758;quiz 5982[PMID:21849487 DOI:10.1182/blood-2011-05-355081]
    14 Reeder CB,Reece DE,Kukreti V,Chen C,Trudel S,Hentz J,Noble B,Pirooz NA,Spong JE,Piza JG,Zepeda VH,Mikhael JR,Leis JF,Bergsagel PL,Fonseca R,Stewart AK.Cyclophosphamide,bortezomib and dexamethasone induction for newly diagnosed multiple myeloma:high response rates in a phase II clinical trial.Leukemia 2009;23:1337-1341[PMID:19225538 DOI:10.1038/leu.2009.26]
    15 Kumar S,Flinn I,Richardson PG,Hari P,Callander N,Noga SJ,Stewart AK,Turturro F,Rifkin R,Wolf J,Estevam J,Mulligan G,Shi H,Webb IJ,Rajkumar SV.Randomized,multicenter,phase 2 study(EVOLUTION)of combinations of bortezomib,dexamethasone,cyclophosphamide,and lenalidomide in previously untreated multiple myeloma.Blood 2012;119:4375-4382[PMID:22422823 DOI:10.1182/blood-2011-11-395749]
    16 Richardson PG,Weller E,Lonial S,Jakubowiak AJ,Jagannath S,Raje NS,Avigan DE,Xie W,Ghobrial IM,Schlossman RL,Mazumder A,Munshi NC,Vesole DH,Joyce R,Kaufman JL,Doss D,Warren DL,Lunde LE,Kaster S,Delaney C,Hideshima T,Mitsiades CS,Knight R,Esseltine DL,Anderson KC.Lenalidomide,bortezomib,and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma.Blood 2010;116:679-686[PMID:20385792DOI:10.1182/blood-2010-02-268862]
    17 Singhal S,Mehta J,Desikan R,Ayers D,Roberson P,Eddlemon P,Munshi N,Anaissie E,Wilson C,Dhodapkar M,Zeddis J,Barlogie B.Antitumor activity of thalidomide in refractory multiple myeloma.N Engl J Med 1999;341:1565-1571[PMID:10564685]
    18 Zhu YX,Braggio E,Shi CX,Bruins LA,Schmidt JE,Van Wier S,Chang XB,Bjorklund CC,Fonseca R,Bergsagel PL,Orlowski RZ,Stewart AK.Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide.Blood 2011;118:4771-4779[PMID:21860026 DOI:10 .1182/blood-2011-05-356063]
    19 Weber D,Rankin K,Gavino M,Delasalle K,Alexanian R.Thalidomide alone or with dexamethasone for previously untreated multiple myeloma.J Clin Oncol 2003;21:16-19[PMID:12506164]
    20 Cavo M,Zamagni E,Tosi P,Cellini C,Cangini D,Tacchetti P,Testoni N,Tonelli M,de Vivo A,Palareti G,Tura S,Baccarani M.First-line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma.Haematologica 2004;89:826-831[PMID:15257934]
    21 Rajkumar SV,Blood E,Vesole D,Fonseca R,Greipp PR.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;24:431-436[PMID:16365178]
    22 Palumbo A,Rajkumar SV,Dimopoulos MA,Richardson PG,San Miguel J,Barlogie B,Harousseau J,Zonder JA,Cavo M,Zangari M,Attal M,Belch A,Knop S,Joshua D,Sezer O,Ludwig H,Vesole D,BladéJ,Kyle R,Westin J,Weber D,Bringhen S,Niesvizky R,Waage A,von Lilienfeld-Toal M,Lonial S,Morgan GJ,Orlowski RZ,Shimizu K,Anderson KC,Boccadoro M,Durie BG,Sonneveld P,Hussein MA.Prevention of thalidomide-and lenalidomide-associated thrombosis in myeloma.Leukemia 2008;22:414-423[PMID:18094721]
    23 Zou Y,Sheng Z,Niu S,Wang H,Yu J,Xu J.Lenalidomide versus thalidomide based regimens as first-line therapy for patients with multiple myeloma.Leuk Lymphoma 2013;54:2219-2225[PMID:23394458 DOI:10.3109/10428194.2013.774393]
    24 Kumar S,Dispenzieri A,Lacy MQ,Hayman SR,Buadi FK,Gastineau DA,Litzow MR,Fonseca R,Roy V,Rajkumar SV,Gertz MA.Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma.Leukemia 2007;21:2035-2042[PMID:17581613]
    25 Ria R,Reale A,Solimando AG,Mangialardi G,Moschetta M,Gelao L,Iodice G,Vacca A.Induction therapy and stem cell mobilization in patients with newly diagnosed multiple myeloma.Stem Cells Int 2012;2012:607260[PMID:22701493DOI:10.1155/2012/607260]
    26 Giralt S,Stadtmauer EA,Harousseau JL,Palumbo A,Bensinger W,Comenzo RL,Kumar S,Munshi NC,Dispenzieri A,Kyle R,Merlini G,San Miguel J,Ludwig H,Hajek R,Jagannath S,Blade J,Lonial S,Dimopoulos MA,Einsele H,Barlogie B,Anderson KC,Gertz M,Attal M,Tosi P,Sonneveld P,Boccadoro M,Morgan G,Sezer O,Mateos MV,Cavo M,Joshua D,Turesson I,Chen W,Shimizu K,Powles R,Richardson PG,Niesvizky R,Rajkumar SV,Durie BG.International myeloma working group(IMWG)consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor(AMD 3100).Leukemia 2009;23:1904-1912[PMID:19554029 DOI:10.1038/leu.2009.127]
    27 San Miguel JF,Schlag R,Khuageva NK,Dimopoulos MA,Shpilberg O,Kropff M,Spicka I,Petrucci MT,Palumbo A,Samoilova OS,Dmoszynska A,Abdulkadyrov KM,Schots R,Jiang B,Mateos MV,Anderson KC,Esseltine DL,Liu K,Cakana A,van de Velde H,Richardson PG.Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.N Engl J Med 2008;359:906-917[PMID:18753647DOI:10.1056/NEJMoa0801479]
    28 Mateos MV,Richardson PG,Schlag R,Khuageva NK,Dimopoulos MA,Shpilberg O,Kropff M,Spicka I,Petrucci MT,Palumbo A,Samoilova OS,Dmoszynska A,Abdulkadyrov KM,Schots R,Jiang B,Esseltine DL,Liu K,Cakana A,van de Velde H,San Miguel JF.Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma:updated followup and impact of subsequent therapy in the phase III VISTA trial.J Clin Oncol 2010;28:2259-2266[PMID:20368561 DOI:10 .1200/JCO.2009.26.0638]
    29 Mateos MV,Oriol A,Martínez-López J,Gutiérrez N,Teruel AI,de Paz R,García-Laraa J,Bengoechea E,Martín A,Mediavilla JD,Palomera L,de Arriba F,González Y,Hernández JM,Sureda A,Bello JL,Bargay J,Pealver FJ,Ribera JM,Martín-Mateos ML,García-Sanz R,Cibeira MT,Ramos ML,Vidriales MB,Paiva B,Montalbán MA,Lahuerta JJ,BladéJ,Miguel JF.Bortezomib,melphalan,and prednisone versus bortezomib,thalidomide,and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma:a randomised trial.Lancet Oncol 2010;11:934-941[PMID:20739218 DOI:10 .1016/S1470-2045(10)70187-X]
    30 Palumbo A,Bringhen S,Rossi D,Cavalli M,Larocca A,Ria R,Offidani M,Patriarca F,Nozzoli C,Guglielmelli T,Benevolo G,Callea V,Baldini L,Morabito F,Grasso M,Leonardi G,Rizzo M,Falcone AP,Gottardi D,Montefusco V,Musto P,Petrucci MT,Ciccone G,Boccadoro M.Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomibmelphalan-prednisone for initial treatment of multiple myeloma:a randomized controlled trial.J Clin Oncol 2010;28:5101-5109[PMID:20940200 DOI:10.1200/JCO.2010.29.8216]
    31 Mateos MV,San Miguel JF.Safety and efficacy of subcutaneous formulation of bortezomib versus the conventional intravenous formulation in multiple myeloma.Ther Adv Hematol 2012;3:117-124[PMID:23556118 DOI:10.1177/2040620711432020]
    32 Gay F,Hayman SR,Lacy MQ,Buadi F,Gertz MA,Kumar S,Dispenzieri A,Mikhael JR,Bergsagel PL,Dingli D,Reeder CB,Lust JA,Russell SJ,Roy V,Zeldenrust SR,Witzig TE,Fonseca R,Kyle RA,Greipp PR,Stewart AK,Rajkumar SV.Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma:a comparative analysis of 411 patients.Blood 2010;115:1343-1350[PMID:20008302 DOI:10.1182/blood-2009-08-239046]
    33 Ludwig H,Hajek R,TóthováE,Drach J,Adam Z,Labar B,Egyed M,Spicka I,Gisslinger H,Greil R,Kuhn I,ZojerN,Hinke A.Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma.Blood 2009;113:3435-3442[PMID:18955563 DOI:10 .1182/blood-2008-07-169565]
    34 Facon T,Mary JY,Hulin C,Benboubker L,Attal M,Pegourie B,Renaud M,Harousseau JL,Guillerm G,Chaleteix C,Dib M,Voillat L,Maisonneuve H,Troncy J,Dorvaux V,Monconduit M,Martin C,Casassus P,Jaubert J,Jardel H,Doyen C,Kolb B,Anglaret B,Grosbois B,Yakoub-Agha I,Mathiot C,AvetLoiseau H.Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma(IFM 99-06):a randomised trial.Lancet2007;370:1209-1218[PMID:17920916]
    35 Hulin C,Facon T,Rodon P,Pegourie B,Benboubker L,Doyen C,Dib M,Guillerm G,Salles B,Eschard JP,Lenain P,Casassus P,Azas I,Decaux O,Garderet L,Mathiot C,Fontan J,Lafon I,Virion JM,Moreau P.Efficacy of melphalan and prednisone plus thalidomide in patients older than 75years with newly diagnosed multiple myeloma:IFM 01/01trial.J Clin Oncol 2009;27:3664-3670[PMID:19451428 DOI:10 .1200/JCO.2008.21.0948]
    36 Palumbo A,Bringhen S,Caravita T,Merla E,Capparella V,Callea V,Cangialosi C,Grasso M,Rossini F,Galli M,Catalano L,Zamagni E,Petrucci MT,De Stefano V,Ceccarelli M,Ambrosini MT,Avonto I,Falco P,Ciccone G,Liberati AM,Musto P,Boccadoro M.Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma:randomised controlled trial.Lancet 2006;367:825-831[PMID:16530576]
    37 Waage A,Gimsing P,Fayers P,Abildgaard N,Ahlberg L,Bjrkstrand B,Carlson K,Dahl IM,Forsberg K,Gulbrandsen N,Hauks E,Hjertner O,Hjorth M,Karlsson T,Knudsen LM,Nielsen JL,Linder O,Mellqvist UH,Nesthus I,Rolke J,Strandberg M,SorboJH,Wisloff F,Juliusson G,Turesson I.Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma.Blood 2010;116:1405-1412[PMID:20448107 DOI:10.1182/blood-2009-08-237974]
    38 Wijermans P,Schaafsma M,Termorshuizen F,Ammerlaan R,Wittebol S,Sinnige H,Zweegman S,van Marwijk Kooy M,van der Griend R,Lokhorst H,Sonneveld P.Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma:the HOVON 49 Study.J Clin Oncol 2010;28:3160-3166[PMID:20516439 DOI:10.1200/JCO.2009.26.1610]
    39 Beksac M,Haznedar R,Firatli-Tuglular T,Ozdogu H,Aydogdu I,Konuk N,Sucak G,Kaygusuz I,Karakus S,Kaya E,Ali R,Gulbas Z,Ozet G,Goker H,Undar L.Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation:results of a randomized trial from the Turkish Myeloma Study Group.Eur J Haematol 2011;86:16-22[PMID:20942865 DOI:10 .1111/j.1600-0609.2010.01524.x]
    40 Kapoor P,Rajkumar SV,Dispenzieri A,Gertz MA,Lacy MQ,Dingli D,Mikhael JR,Roy V,Kyle RA,Greipp PR,Kumar S,Mandrekar SJ.Melphalan and prednisone versus melphalan,prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma:a meta-analysis.Leukemia 2011;25:689-696[PMID:21233832 DOI:10.1038/leu.2010.313]
    41 Fayers PM,Palumbo A,Hulin C,Waage A,Wijermans P,BeksaM,Bringhen S,Mary JY,Gimsing P,Termorshuizen F,Haznedar R,Caravita T,Moreau P,Turesson I,Musto P,Benboubker L,Schaafsma M,Sonneveld P,Facon T.Thalidomide for previously untreated elderly patients with multiple myeloma:meta-analysis of 1685 individual patient data from6 randomized clinical trials.Blood 2011;118:1239-1247[PMID:21670471 DOI:10.1182/blood-2011-03-341669]
    42 Zonder JA,Crowley J,Hussein MA,Bolejack V,Moore DF,Whittenberger BF,Abidi MH,Durie BG,Barlogie B.Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma:a randomized Southwest Oncology Group trial(S0232).Blood 2010;116:5838-5841[PMID:20876454 DOI:10.1182/blood-2010-08-303487]
    43 Rajkumar SV,Jacobus S,Callander NS,Fonseca R,Vesole DH,Williams ME,Abonour R,Siegel DS,Katz M,Greipp PR.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;11:29-37[PMID:19853510 DOI:10.1016/S1470-2045(09)70284-0]
    44 Jacobus S,Callander N,Siegel D,Abonour R,David D,Fonseca R,Williams M,Katz M,Greipp P,Rajkumar V.Outcome of elderly patients 70 years and older with newly diagnosed myeloma in the ECOG randomized trial of lenalidomide/high-dose dexamethasone(RD)versus lenalidomide/lowdose dexamethasone(Rd)[abstract].Haematologica 2010;95(Suppl 2):370
    45 Palumbo A,Hajek R,Delforge M,Kropff M,Petrucci MT,Catalano J,Gisslinger H,Wiktor-Jdrzejczak W,Zodelava M,Weisel K,Cascavilla N,Iosava G,Cavo M,Kloczko J,BladéJ,Beksac M,Spicka I,Plesner T,Radke J,Langer C,Ben Yehuda D,Corso A,Herbein L,Yu Z,Mei J,Jacques C,Dimopoulos MA.Continuous lenalidomide treatment for newly diagnosed multiple myeloma.N Engl J Med 2012;366:1759-1769[PMID:22571200 DOI:10.1056/NEJMoa1112704]
    46 Barlogie B,Anaissie E,van Rhee F,Haessler J,Hollmig K,Pineda-Roman M,Cottler-Fox M,Mohiuddin A,Alsayed Y,Tricot G,Bolejack V,Zangari M,Epstein J,Petty N,Steward D,Jenkins B,Gurley J,Sullivan E,Crowley J,Shaughnessy JD.Incorporating bortezomib into upfront treatment for multiple myeloma:early results of total therapy 3.Br J Haematol 2007;138:176-185[PMID:17593024]
    47 Rajkumar SV,Gahrton G,Bergsagel PL.Approach to the treatment of multiple myeloma:a clash of philosophies.Blood 2011;118:3205-3211[PMID:21791430 DOI:10.1182/blood-2011-06-297853]
    48 Rajkumar SV.Treatment of myeloma:cure vs control.Mayo Clin Proc 2008;83:1142-1145[PMID:18828974 DOI:10 .4065/83.10.1142]
    49 Mikhael JR,Dingli D,Roy V,Reeder CB,Buadi FK,Hayman SR,Dispenzieri A,Fonseca R,Sher T,Kyle RA,Lin Y,Russell SJ,Kumar S,Bergsagel PL,Zeldenrust SR,Leung N,Drake MT,Kapoor P,Ansell SM,Witzig TE,Lust JA,Dalton RJ,Gertz MA,Stewart AK,Rajkumar SV,Chanan-Khan A,Lacy MQ.Management of newly diagnosed symptomatic multiple myeloma:updated Mayo Stratification of Myeloma and Risk-Adapted Therapy(m SMART)consensus guidelines 2013.Mayo Clin Proc 2013;88:360-376[PMID:23541011DOI:10.1016/j.mayocp.2013.01.019]
    50 Moreau P,Pylypenko H,Grosicki S,Karamanesht I,Leleu X,Grishunina M,Rekhtman G,Masliak Z,Robak T,Shubina A,Arnulf B,Kropff M,Cavet J,Esseltine DL,Feng H,Girgis S,van de Velde H,Deraedt W,Harousseau JL.Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma:a randomised,phase 3,non-inferiority study.Lancet Oncol 2011;12:431-440[PMID:21507715 DOI:10.1016/S1470-2045(11)70081-X]
    51 Nair B,van Rhee F,Shaughnessy JD,Anaissie E,Szymonifka J,Hoering A,Alsayed Y,Waheed S,Crowley J,Barlogie B.Superior results of Total Therapy 3(2003-33)in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance.Blood 2010;115:4168-4173[PMID:20124509 DOI:10.1182/blood-2009-11-255620]
    52 San-Miguel J,Harousseau JL,Joshua D,Anderson KC.Individualizing treatment of patients with myeloma in theera of novel agents.J Clin Oncol 2008;26:2761-2766[PMID:18427148 DOI:10.1200/JCO.2007.15.2546]
    53 Palumbo A,Bringhen S,Ludwig H,Dimopoulos MA,BladéJ,Mateos MV,Rosiol L,Boccadoro M,Cavo M,Lokhorst H,Zweegman S,Terpos E,Davies F,Driessen C,Gimsing P,Gramatzki M,Hàjek R,Johnsen HE,Leal Da Costa F,Sezer O,Spencer A,Beksac M,Morgan G,Einsele H,San Miguel JF,Sonneveld P.Personalized therapy in multiple myeloma according to patient age and vulnerability:a report of the European Myeloma Network(EMN).Blood 2011;118:4519-4529[PMID:21841166 DOI:10.1182/blood-2011-06-358812]
    54 Barlogie B,Alexanian R,Dicke KA,Zagars G,Spitzer G,Jagannath S,Horwitz L.High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma.Blood 1987;70:869-872[PMID:3304465]
    55 Barlogie B,Hall R,Zander A,Dicke K,Alexanian R.Highdose melphalan with autologous bone marrow transplantation for multiple myeloma.Blood 1986;67:1298-1301[PMID:3516252]
    56 Alexanian R,Barlogie B,Dixon D.High-dose glucocorticoid treatment of resistant myeloma.Ann Intern Med 1986;105:8 -11[PMID:3717812]
    57 Gertz MA,Garton JP,Greipp PR,Witzig TE,Kyle RA.A phase II study of high-dose methylprednisolone in refractory or relapsed multiple myeloma.Leukemia 1995;9:2115-2118[PMID:8609725]
    58 Durie BG,Dixon DO,Carter S,Stephens R,Rivkin S,Bonnet J,Salmon SE,Dabich L,Files JC,Costanzi JJ.Improved survival duration with combination chemotherapy induction for multiple myeloma:a Southwest Oncology Group Study.J Clin Oncol 1986;4:1227-1237[PMID:3525768]
    59 Giles FJ,Wickham NR,Rapoport BL,Somlo G,Lim SW,Shan J,Lynott AM.Cyclophosphamide,etoposide,vincristine,adriamycin,and dexamethasone(CEVAD)regimen in refractory multiple myeloma:an International Oncology Study Group(IOSG)phase II protocol.Am J Hematol 2000;63 :125-130[PMID:10679801]
    60 Dadacaridou M,Papanicolaou X,Maltesas D,Megalakaki C,Patos P,Panteli K,Repousis P,Mitsouli-Mentzikof C.Dexamethasone,cyclophosphamide,etoposide and cisplatin(DCEP)for relapsed or refractory multiple myeloma patients.J BUON 2007;12:41-44[PMID:17436400]
    61 Lee CK,Barlogie B,Munshi N,Zangari M,Fassas A,Jacobson J,van Rhee F,Cottler-Fox M,Muwalla F,Tricot G.DTPACE:an effective,novel combination chemotherapy with thalidomide for previously treated patients with myeloma.J Clin Oncol 2003;21:2732-2739[PMID:12860952]
    62 Garban F,Attal M,Michallet M,Hulin C,Bourhis JH,Yakoub-Agha I,Lamy T,Marit G,Maloisel F,Berthou C,Dib M,Caillot D,Deprijck B,Ketterer N,Harousseau JL,Sotto JJ,Moreau P.Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft(IFM99-03 trial)with tandem autologous stem cell transplantation(IFM99-04 trial)in high-risk de novo multiple myeloma.Blood 2006;107:3474-3480[PMID:16397129]
    63 Kroger N,Perez-Simon JA,Myint H,Klingemann H,Shimoni A,Nagler A,Martino R,Alegre A,Tomas JF,Schwerdtfeger R,Kiehl M,Fauser A,Sayer HG,Leon A,Beyer J,Zabelina T,Ayuk F,San Miguel JF,Brand R,Zander AR.Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma.Biol Blood Marrow Transplant 2004;10:698-708[PMID:15389436]
    64 Elice F,Raimondi R,Tosetto A,D’Emilio A,Di Bona E,Piccin A,Rodeghiero F.Prolonged overall survival with second on-demand autologous transplant in multiple myeloma.Am J Hematol 2006;81:426-431[PMID:16680735]
    65 Olin RL,Vogl DT,Porter DL,Luger SM,Schuster SJ,Tsai DE,Siegel DL,Cook RJ,Mangan PA,Cunningham K,Stadtmauer EA.Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma.Bone Marrow Transplant 2009;43:417-422[PMID:18850013 DOI:10.1038/bmt.2008.334]
    66 Glasmacher A,Hahn C,Hoffmann F,Naumann R,Goldschmidt H,von Lilienfeld-Toal M,Orlopp K,Schmidt-Wolf I,Gorschlüter M.A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma.Br J Haematol 2006;132:584-593[PMID:16445831]
    67 Kropff M,Baylon HG,Hillengass J,Robak T,Hajek R,Liebisch P,Goranov S,Hulin C,BladéJ,Caravita T,AvetLoiseau H,Moehler TM,Pattou C,Lucy L,Kueenburg E,Glasmacher A,Zerbib R,Facon T.Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma:results from OPTIMUM,a randomized trial.Haematologica 2012;97:784-791[PMID:22133776 DOI:10 .3324/haematol.2011.044271]
    68 Anagnostopoulos A,Weber D,Rankin K,Delasalle K,Alexanian R.Thalidomide and dexamethasone for resistant multiple myeloma.Br J Haematol 2003;121:768-771[PMID:12780791]
    69 Kropff MH,Lang N,Bisping G,DominéN,Innig G,Hentrich M,Mitterer M,Südhoff T,Fenk R,Straka C,Heinecke A,Koch OM,Ostermann H,Berdel WE,Kienast J.Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide(Hyper CDT)in primary refractory or relapsed multiple myeloma.Br J Haematol 2003;122 :607-616[PMID:12899716]
    70 Sidra G,Williams CD,Russell NH,Zaman S,Myers B,Byrne JL.Combination chemotherapy with cyclophosphamide,thalidomide and dexamethasone for patients with refractory,newly diagnosed or relapsed myeloma.Haematologica 2006;91 :862-863[PMID:16769594]
    71 Offidani M,Marconi M,Corvatta L,Olivieri A,Catarini M,Leoni P.Thalidomide plus oral melphalan for advanced multiple myeloma:a phase II study.Haematologica 2003;88:1432-1433[PMID:14688003]
    72 Srkalovic G,Elson P,Trebisky B,Karam MA,Hussein MA.Use of melphalan,thalidomide,and dexamethasone in treatment of refractory and relapsed multiple myeloma.Med Oncol 2002;19:219-226[PMID:12512915]
    73 Offidani M,Corvatta L,Marconi M,Visani G,Alesiani F,Brunori M,Galieni P,Catarini M,Burattini M,Centurioni R,Rupoli S,Scortechini AR,Giuliodori L,Candela M,Capelli D,Montanari M,Olivieri A,Piersantelli MN,Leoni P.Lowdose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma:a prospective,multicenter,phase II study.Haematologica 2006;91:133-136[PMID:16434383]
    74 Hussein MA,Baz R,Srkalovic G,Agrawal N,Suppiah R,Hsi E,Andresen S,Karam MA,Reed J,Faiman B,Kelly M,Walker E.Phase 2 study of pegylated liposomal doxorubicin,vincristine,decreased-frequency dexamethasone,and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma.Mayo Clin Proc 2006;81:889-895[PMID:16835968]
    75 Moehler TM,Neben K,Benner A,Egerer G,Krasniqi F,Ho AD,Goldschmidt H.Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy.Blood 2001;98:3846-3848[PMID:11739195]
    76 Orlowski RZ,Stinchcombe TE,Mitchell BS,Shea TC,Baldwin AS,Stahl S,Adams J,Esseltine DL,Elliott PJ,Pien CS,Guerciolini R,Anderson JK,Depcik-Smith ND,Bhagat R,Lehman MJ,Novick SC,O’Connor OA,Soignet SL.Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies.J Clin Oncol 2002;20:4420-4427[PMID:12431963]
    77 Richardson PG,Barlogie B,Berenson J,Singhal S,Jagannath S,Irwin D,Rajkumar SV,Srkalovic G,Alsina M,Alexanian R,Siegel D,Orlowski RZ,Kuter D,Limentani SA,Lee S,Hideshima T,Esseltine DL,Kauffman M,Adams J,Schenkein DP,Anderson KC.A phase 2 study of bortezomib in relapsed,refractory myeloma.N Engl J Med 2003;348:2609-2617[PMID:12826635]
    78 Richardson PG,Sonneveld P,Schuster M,Irwin D,Stadtmauer E,Facon T,Harousseau JL,Ben-Yehuda D,Lonial S,Goldschmidt H,Reece D,Miguel JS,BladéJ,Boccadoro M,Cavenagh J,Alsina M,Rajkumar SV,Lacy M,Jakubowiak A,Dalton W,Boral A,Esseltine DL,Schenkein D,Anderson KC.Extended follow-up of a phase 3 trial in relapsed multiple myeloma:final time-to-event results of the APEX trial.Blood 2007;110:3557-3560[PMID:17690257]
    79 Orlowski RZ,Nagler A,Sonneveld P,BladéJ,Hajek R,Spencer A,San Miguel J,Robak T,Dmoszynska A,Horvath N,Spicka I,Sutherland HJ,Suvorov AN,Zhuang SH,Parekh T,Xiu L,Yuan Z,Rackoff W,Harousseau JL.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;25:3892-3901[PMID:17679727]
    80 Jakubowiak AJ,Kendall T,Al-Zoubi A,Khaled Y,Mineishi S,Ahmed A,Campagnaro E,Brozo C,Braun T,Talpaz M,Kaminski MS.Phase II trial of combination therapy with bortezomib,pegylated liposomal doxorubicin,and dexamethasone in patients with newly diagnosed myeloma.J Clin Oncol 2009;27:5015-5022[PMID:19738129 DOI:10 .1200/JCO.2008.19.5370]
    81 Berenson JR,Yang HH,Sadler K,Jarutirasarn SG,Vescio RA,Mapes R,Purner M,Lee SP,Wilson J,Morrison B,Adams J,Schenkein D,Swift R.Phase I/II trial assessing bortezomib and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma.J Clin Oncol 2006;24:937-944[PMID:16418495]
    82 Reece DE,Rodriguez GP,Chen C,Trudel S,Kukreti V,Mikhael J,Pantoja M,Xu W,Stewart AK.Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma.J Clin Oncol 2008;26:4777-4783[PMID:18645194 DOI:10.1200/JCO.2007.14.2372]
    83 Richardson P,Jagannath S,Hussein M,Berenson J,Singhal S,Irwin D,Williams SF,Bensinger W,Badros AZ,Vescio R,Kenvin L,Yu Z,Olesnyckyj M,Zeldis J,Knight R,Anderson KC.Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma.Blood 2009;114:772-778[PMID:19471019 DOI:10.1182/blood-2008-12-196238]
    84 Weber DM,Chen C,Niesvizky R,Wang M,Belch A,Stadtmauer EA,Siegel D,Borrello I,Rajkumar SV,Chanan-Khan AA,Lonial S,Yu Z,Patin J,Olesnyckyj M,Zeldis JB,Knight RD.Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America.N Engl J Med 2007;357:2133-2142[PMID:18032763]
    85 Dimopoulos M,Spencer A,Attal M,Prince HM,Harousseau JL,Dmoszynska A,San Miguel J,Hellmann A,Facon T,FoàR,Corso A,Masliak Z,Olesnyckyj M,Yu Z,Patin J,Zeldis JB,Knight RD.Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma.N Engl J Med 2007;357 :2123-2132[PMID:18032762]
    86 Dimopoulos MA,Chen C,Spencer A,Niesvizky R,Attal M,Stadtmauer EA,Petrucci MT,Yu Z,Olesnyckyj M,Zeldis JB,Knight RD,Weber DM.Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.Leukemia 2009;23:2147-2152[PMID:19626046 DOI:10.1038/leu.2009.147]
    87 Touzeau C,Blin N,Clavert A,Roland V,Loirat M,Tessoulin B,Le Gouill S,Planche L,Pennetier M,Mahe B,Mohty M,Malard F,Peterlin P,Dubruille V,Moreau P.Efficacy of lenalidomide plus dexamethasone in patients older than 75years with relapsed multiple myeloma.Leuk Lymphoma 2012;53 :1318-1320[PMID:22211836 DOI:10.3109/10428194.2011.654116]
    88 Baz R,Walker E,Karam MA,Choueiri TK,Jawde RA,Bruening K,Reed J,Faiman B,Ellis Y,Brand C,Srkalovic G,Andresen S,Knight R,Zeldis J,Hussein MA.Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma:safety and efficacy.Ann Oncol 2006;17:1766-1771[PMID:16980599]
    89 Knop S,Gerecke C,Liebisch P,Topp MS,Platzbecker U,Sezer O,Vollmuth C,Falk K,Glasmacher A,Maeder U,Einsele H,Bargou RC.Lenalidomide,adriamycin,and dexamethasone(RAD)in patients with relapsed and refractory multiple myeloma:a report from the German Myeloma Study Group DSMM(Deutsche Studiengruppe Multiples Myelom).Blood 2009;113:4137-4143[PMID:19182205 DOI:10 .1182/blood-2008-10-184135]
    90 van de Donk NW,Wittebol S,Minnema MC,Lokhorst HM.Lenalidomide(Revlimid)combined with continuous oral cyclophosphamide(endoxan)and prednisone(REP)is effective in lenalidomide/dexamethasone-refractory myeloma.Br J Haematol 2010;148:335-337[PMID:20085583 DOI:10.1111/j.1365-2141.2009.07931.x]
    91 Morgan GJ,Schey SA,Wu P,Srikanth M,Phekoo KJ,Jenner M,Davies FE.Lenalidomide(Revlimid),in combination with cyclophosphamide and dexamethasone(RCD),is an effective and tolerated regimen for myeloma patients.Br J Haematol 2007;137:268-269[PMID:17408469]
    92 Ciolli S,Leoni F,Casini C,Breschi C,Santini V,Bosi A.The addition of liposomal doxorubicin to bortezomib,thalidomide and dexamethasone significantly improves clinical outcome of advanced multiple myeloma.Br J Haematol 2008;141:814-819[PMID:18410447 DOI:10.1111/j.1365-2141.2008.07147.x]
    93 Terpos E,Kastritis E,Roussou M,Heath D,Christoulas D,Anagnostopoulos N,Eleftherakis-Papaiakovou E,Tsionos K,Croucher P,Dimopoulos MA.The combination of bortezomib,melphalan,dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis.Leukemia 2008;22:2247-2256[PMID:18769451 DOI:10.1038/leu.2008.235]
    94 Palumbo A,Ambrosini MT,Benevolo G,Pregno P,Pescosta N,Callea V,Cangialosi C,Caravita T,Morabito F,Musto P,Bringhen S,Falco P,Avonto I,Cavallo F,Boccadoro M.Bortezomib,melphalan,prednisone,and thalidomide for relapsed multiple myeloma.Blood 2007;109:2767-2772[PMID:17148584]
    95 Pineda-Roman M,Zangari M,van Rhee F,Anaissie E,Szymonifka J,Hoering A,Petty N,Crowley J,Shaughnessy J,Epstein J,Barlogie B.VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma.Leukemia 2008;22 :1419-1427[PMID:18432260 DOI:10.1038/leu.2008.99]
    96 Richardson PG,Weller E,Jagannath S,Avigan DE,Alsina M,Schlossman RL,Mazumder A,Munshi NC,Ghobrial IM,Doss D,Warren DL,Lunde LE,Mc Kenney M,Delaney C,Mitsiades CS,Hideshima T,Dalton W,Knight R,Esseltine DL,Anderson KC.Multicenter,phase I,dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma.J Clin Oncol 2009;27:5713-5719[PMID:19786667 DOI:10.1200/JCO.2009.22.2679]
    97 Palumbo A,Larocca A,Falco P,Sanpaolo G,Falcone AP,Federico V,Canepa L,Crugnola M,Genuardi M,Magarotto V,Petrucci MT,Boccadoro M.Lenalidomide,melphalan,prednisone and thalidomide(RMPT)for relapsed/refractory multiple myeloma.Leukemia 2010;24:1037-1042[PMID:20376079 DOI:10.1038/leu.2010.58]
    98 Cunningham D,Powles R,Malpas J,Raje N,Milan S,Viner C,Montes A,Hickish T,Nicolson M,Johnson P,TreleavenJ,Raymond J,Gore M.A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma:long-term follow-up results.Br J Haematol 1998;102 :495-502[PMID:9695964]
    99 Attal M,Harousseau JL,Leyvraz S,Doyen C,Hulin C,Benboubker L,Yakoub Agha I,Bourhis JH,Garderet L,Pegourie B,Dumontet C,Renaud M,Voillat L,Berthou C,Marit G,Monconduit M,Caillot D,Grobois B,Avet-Loiseau H,Moreau P,Facon T.Maintenance therapy with thalidomide improves survival in patients with multiple myeloma.Blood2006;108:3289-3294[PMID:16873668]
    100 Mc Carthy PL,Owzar K,Hofmeister CC,Hurd DD,Hassoun H,Richardson PG,Giralt S,Stadtmauer EA,Weisdorf DJ,Vij R,Moreb JS,Callander NS,Van Besien K,Gentile T,Isola L,Maziarz RT,Gabriel DA,Bashey A,Landau H,Martin T,Qazilbash MH,Levitan D,Mc Clune B,Schlossman R,Hars V,Postiglione J,Jiang C,Bennett E,Barry S,Bressler L,Kelly M,Seiler M,Rosenbaum C,Hari P,Pasquini MC,Horowitz MM,Shea TC,Devine SM,Anderson KC,Linker C.Lenalidomide after stem-cell transplantation for multiple myeloma.N Engl J Med 2012;366:1770-1781[PMID:22571201 DOI:10 .1056/NEJMoa1114083]
    101 Attal M,Lauwers-Cances V,Marit G,Caillot D,Moreau P,Facon T,Stoppa AM,Hulin C,Benboubker L,Garderet L,Decaux O,Leyvraz S,Vekemans MC,Voillat L,Michallet M,Pegourie B,Dumontet C,Roussel M,Leleu X,Mathiot C,Payen C,Avet-Loiseau H,Harousseau JL.Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.N Engl J Med 2012;366:1782-1791[PMID:22571202DOI:10.1056/NEJMoa1114138]
    102 Scheid C,Sonneveld P,Schmidt-Wolf IG,van der Holt B,el Jarari L,Bertsch U,Salwender H,Zweegman S,Blau IW,Vellenga E,Weisel K,Pfreundschuh M,Jie KS,Neben K,van de Velde H,Duehrsen U,Schaafsma MR,Lindemann W,Kersten MJ,Peter N,Hnel M,Croockewit S,Martin H,Wittebol S,Bos GM,van Marwijk-Kooy M,Wijermans P,Goldschmidt H,Lokhorst HM.Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma:a subgroup analysis from the HOVON-65/GMMG-HD4 trial.Haematologica 2014;99:148-154[PMID:23996482]
    103 Lopez-Girona A,Mendy D,Ito T,Miller K,Gandhi AK,Kang J,Karasawa S,Carmel G,Jackson P,Abbasian M,Mahmoudi A,Cathers B,Rychak E,Gaidarova S,Chen R,Schafer PH,Handa H,Daniel TO,Evans JF,Chopra R.Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.Leukemia 2012;26:2326-2335[PMID:22552008 DOI:10.1038/leu.2012.119]
    104 Gertz MA.Pomalidomide and myeloma meningitis.Leuk Lymphoma 2013;54:681-682[PMID:22917017 DOI:10.3109/10428194.2012.723708]
    105 Zhu YX,Kortuem KM,Stewart AK.Molecular mechanism of action of immune-modulatory drugs thalidomide,lenalidomide and pomalidomide in multiple myeloma.Leuk Lymphoma 2013;54:683-687[PMID:22966948 DOI:10.3109/10428194.2012.728597]
    106 Escoubet-Lozach L,Lin IL,Jensen-Pergakes K,Brady HA,Gandhi AK,Schafer PH,Muller GW,Worland PJ,Chan KW,Verhelle D.Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism.Cancer Res 2009;69:7347-7356[PMID:19738071 DOI:10 .1158/0008-5472.CAN-08-4898]
    107 Schey SA,Fields P,Bartlett JB,Clarke IA,Ashan G,Knight RD,Streetly M,Dalgleish AG.Phase I study of an immunomodulatory thalidomide analog,CC-4047,in relapsed or refractory multiple myeloma.J Clin Oncol 2004;22:3269-3276[PMID:15249589]
    108 Streetly MJ,Gyertson K,Daniel Y,Zeldis JB,Kazmi M,Schey SA.Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation.Br J Haematol 2008;141:41-51[PMID:18324965 DOI:10.1111/j.1365-2141.2008.07013.x]
    109 Richardson PG,Siegel D,Baz R,Kelley SL,Munshi NC,Laubach J,Sullivan D,Alsina M,Schlossman R,Ghobrial IM,Doss D,Loughney N,Mc Bride L,Bilotti E,Anand P,Nardelli L,Wear S,Larkins G,Chen M,Zaki MH,Jacques C,Anderson KC.Phase 1 study of pomalidomide MTD,safety,and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib.Blood 2013;121:1961-1967[PMID:23243282 DOI:10.1182/blood-2012-08-450742]
    110 Leleu X,Attal M,Arnulf B,Moreau P,Traulle C,Marit G,Mathiot C,Petillon MO,Macro M,Roussel M,Pegourie B,Kolb B,Stoppa AM,Hennache B,Bréchignac S,Meuleman N,Thielemans B,Garderet L,Royer B,Hulin C,Benboubker L,Decaux O,Escoffre-Barbe M,Michallet M,Caillot D,Fermand JP,Avet-Loiseau H,Facon T.Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma:Intergroupe Francophone du Myélome 2009-02.Blood 2013;121:1968-1975[PMID:23319574 DOI:10.1182/blood-2012-09-452375]
    111 Short KD,Rajkumar SV,Larson D,Buadi F,Hayman S,Dispenzieri A,Gertz M,Kumar S,Mikhael J,Roy V,Kyle RA,Lacy MQ.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 :906-908[PMID:21350560 DOI:10.1038/leu.2011.29]
    112 Lacy MQ,Allred JB,Gertz MA,Hayman SR,Short KD,Buadi F,Dispenzieri A,Kumar S,Greipp PR,Lust JA,Russell SJ,Dingli D,Zeldenrust S,Fonseca R,Bergsagel PL,Roy V,Stewart AK,Laumann K,Mandrekar SJ,Reeder C,Rajkumar SV,Mikhael JR.Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide:comparison of 2 dosing strategies in dual-refractory disease.Blood 2011;118:2970-2975[PMID:21690557 DOI:10 .1182/blood-2011-04-348896]
    113 Geyer HL,Viggiano RW,Lacy MQ,Witzig TE,Leslie KO,Mikhael JR,Stewart K.Acute lung toxicity related to pomalidomide.Chest 2011;140:529-533[PMID:21813533DOI:10.1378/chest.10-2082]
    114 Demo SD,Kirk CJ,Aujay MA,Buchholz TJ,Dajee M,Ho MN,Jiang J,Laidig GJ,Lewis ER,Parlati F,Shenk KD,Smyth MS,Sun CM,Vallone MK,Woo TM,Molineaux CJ,Bennett MK.Antitumor activity of PR-171,a novel irreversible inhibitor of the proteasome.Cancer Res 2007;67:6383-6391[PMID:17616698]
    115 O’Connor OA,Stewart AK,Vallone M,Molineaux CJ,Kunkel LA,Gerecitano JF,Orlowski RZ.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 :7085-7091[PMID:19903785 DOI:10.1158/1078-0432.CCR-09-0822]
    116 Alsina M,Trudel S,Furman RR,Rosen PJ,O’Connor OA,Comenzo RL,Wong A,Kunkel LA,Molineaux CJ,Goy A.A phase I single-agent study of twice-weekly consecutive-day dosing of the proteasome inhibitor carfilzomib in patients with relapsed or refractory multiple myeloma or lymphoma.Clin Cancer Res 2012;18:4830-4840[PMID:22761464]
    117 Vij R,Wang M,Kaufman JL,Lonial S,Jakubowiak AJ,Stewart AK,Kukreti V,Jagannath S,Mc Donagh KT,Alsina M,Bahlis NJ,Reu FJ,Gabrail NY,Belch A,Matous JV,Lee P,Rosen P,Sebag M,Vesole DH,Kunkel LA,Wear SM,Wong AF,Orlowski RZ,Siegel DS.An open-label,singlearm,phase 2(PX-171-004)study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refrac-tory multiple myeloma.Blood 2012;119:5661-5670[PMID:22555973 DOI:10.1182/blood-2012-03-414359]
    118 Siegel DS,Martin T,Wang M,Vij R,Jakubowiak AJ,Lonial S,Trudel S,Kukreti V,Bahlis N,Alsina M,Chanan-Khan A,Buadi F,Reu FJ,Somlo G,Zonder J,Song K,Stewart AK,Stadtmauer E,Kunkel L,Wear S,Wong AF,Orlowski RZ,Jagannath S.A phase 2 study of single-agent carfilzomib(PX-171 -003-A1)in patients with relapsed and refractory multiple myeloma.Blood 2012;120:2817-2825[PMID:22833546DOI:10.1182/blood-2012-05-425934]
    119 Siegel D,Martin T,Nooka A,Harvey RD,Vij R,Niesvizky R,Badros AZ,Jagannath S,Mc Culloch L,Rajangam K,Lonial S.Integrated safety profile of single-agent carfilzomib:experience from 526 patients enrolled in 4 phase II clinical studies.Haematologica 2013;98:1753-1761[PMID:23935022 DOI:10 .3324/haematol.2013.089334]
    120 Papadopoulos KP,Burris HA,Gordon M,Lee P,Sausville EA,Rosen PJ,Patnaik A,Cutler RE,Wang Z,Lee S,Jones SF,Infante JR.A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.Cancer Chemother Pharmacol 2013;72:861-868[PMID:23975329 DOI:10 .1007/s00280-013-2267-x]
    121 Niesvizky R,Martin TG,Bensinger WI,Alsina M,Siegel DS,Kunkel LA,Wong AF,Lee S,Orlowski RZ,Wang M.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;19:2248-2256[PMID:23447001 DOI:10.1158/1078-0432.CCR-12-3352]
    122 Jakubowiak AJ,Dytfeld D,Griffith KA,Lebovic D,Vesole DH,Jagannath S,Al-Zoubi A,Anderson T,Nordgren B,Detweiler-Short K,Stockerl-Goldstein K,Ahmed A,Jobkar T,Durecki DE,Mc Donnell K,Mietzel M,Couriel D,Kaminski M,Vij R.A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma.Blood 2012;120:1801-1809[PMID:22665938 DOI:10.1182/blood-2012-04-422683]
    123 Mikhael JR,Reeder CB,Libby EN III,Costa LJ,Bergsagel PL,Buadi F,Mayo A,Gano K,Wolf C,Dueck AC,Stewart AK.A phase I/II trial of cyclophosphamide,carfilzomib,thalidomide,and dexamethasone(CYCLONE)in patients with newly diagnosed multiple myeloma.ASCO Annual Meeting Abstracts 2012;30 Suppl 15:8010
    124 Anderson KC,Carrasco RD.Pathogenesis of myeloma.Annu Rev Pathol 2011;6:249-274[PMID:21261519 DOI:10 .1146/annurev-pathol-011110-130249]
    125 Hideshima T,Mitsiades C,Tonon G,Richardson PG,Anderson KC.Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets.Nat Rev Cancer 2007;7:585-598[PMID:17646864]
    126 Ria R,Reale A,De Luisi A,Ferrucci A,Moschetta M,Vacca A.Bone marrow angiogenesis and progression in multiple myeloma.Am J Blood Res 2011;1:76-89[PMID:22432068]
    127 Berardi S,Caivano A,Ria R,Nico B,Savino R,Terracciano R,De Tullio G,Ferrucci A,De Luisi A,Moschetta M,Mangialardi G,Catacchio I,Basile A,Guarini A,Zito A,Ditonno P,Musto P,Dammacco F,Ribatti D,Vacca A.Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets.Oncogene 2012;31:2258-2269[PMID:21963844 DOI:10 .1038/onc.2011.412]
    128 Chauhan D,Catley L,Li G,Podar K,Hideshima T,Velankar M,Mitsiades C,Mitsiades N,Yasui H,Letai A,Ovaa H,Berkers C,Nicholson B,Chao TH,Neuteboom ST,Richardson P,Palladino MA,Anderson KC.A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib.Cancer Cell2005;8:407-419[PMID:16286248]
    129 Chauhan D,Singh A,Brahmandam M,Podar K,Hideshima T,Richardson P,Munshi N,Palladino MA,Anderson KC.Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma.Blood 2008;111:1654-1664[PMID:18006697]
    130 Ocio EM,Mateos MV,Maiso P,Pandiella A,San-Miguel JF.New drugs in multiple myeloma:mechanisms of action and phase I/II clinical findings.Lancet Oncol 2008;9:1157-1165[PMID:19038762 DOI:10.1016/S1470-2045(08)70304-8]
    131 Mitsiades N,Mitsiades CS,Richardson PG,Mc Mullan C,Poulaki V,Fanourakis G,Schlossman R,Chauhan D,Munshi NC,Hideshima T,Richon VM,Marks PA,Anderson KC.Molecular sequelae of histone deacetylase inhibition in human malignant B cells.Blood 2003;101:4055-4062[PMID:12531799]
    132 Dokmanovic M,Clarke C,Marks PA.Histone deacetylase inhibitors:overview and perspectives.Mol Cancer Res 2007;5:981 -989[PMID:17951399]
    133 Mitsiades CS,Mitsiades NS,Mc Mullan CJ,Poulaki V,Shringarpure R,Hideshima T,Akiyama M,Chauhan D,Munshi N,Gu X,Bailey C,Joseph M,Libermann TA,Richon VM,Marks PA,Anderson KC.Transcriptional signature of histone deacetylase inhibition in multiple myeloma:biological and clinical implications.Proc Natl Acad Sci USA 2004;101:540 -545[PMID:14695887]
    134 Badros A,Burger AM,Philip S,Niesvizky R,Kolla SS,Goloubeva O,Harris C,Zwiebel J,Wright JJ,Espinoza-Delgado I,Baer MR,Holleran JL,Egorin MJ,Grant S.Phase I study of vorinostat in combination with bortezomib for relapsed and refractory multiple myeloma.Clin Cancer Res 2009;15 :5250-5257[PMID:19671864 DOI:10.1158/1078-0432.CCR-08-2850]
    135 Kawauchi K,Ogasawara T,Yasuyama M,Otsuka K,Yamada O.The PI3K/Akt pathway as a target in the treatment of hematologic malignancies.Anticancer Agents Med Chem 2009;9 :550-559[PMID:19519296]
    136 Hideshima T,Catley L,Yasui H,Ishitsuka K,Raje N,Mitsiades C,Podar K,Munshi NC,Chauhan D,Richardson PG,Anderson KC.Perifosine,an oral bioactive novel alkylphospholipid,inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells.Blood 2006;107:4053-4062[PMID:16418332]
    137 Richardson PG,Wolf J,Jakubowiak A,Zonder J,Lonial S,Irwin D,Densmore J,Krishnan A,Raje N,Bar M,Martin T,Schlossman R,Ghobrial IM,Munshi N,Laubach J,Allerton J,Hideshima T,Colson K,Poradosu E,Gardner L,Sportelli P,Anderson KC.Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib:results of a multicenter phase I/II trial.J Clin Oncol 2011;29:4243-4249[PMID:21990396 DOI:10.1200/JCO.2010.33.9788]
    138 Dowling RJ,Topisirovic I,Fonseca BD,Sonenberg N.Dissecting the role of m TOR:lessons from m TOR inhibitors.Biochim Biophys Acta 2010;1804:433-439[PMID:20005306DOI:10.1016/j.bbapap.2009.12.001]
    139 Farag SS,Zhang S,Jansak BS,Wang X,Kraut E,Chan K,Dancey JE,Grever MR.Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma.Leuk Res 2009;33:1475-1480[PMID:19261329 DOI:10.1016/j.leukres.2009.01.039]
    140 Ghobrial IM,Weller E,Vij R,Munshi NC,Banwait R,Bagshaw M,Schlossman R,Leduc R,Chuma S,Kunsman J,Laubach J,Jakubowiak AJ,Maiso P,Roccaro A,Armand P,Dollard A,Warren D,Harris B,Poon T,Sam A,Rodig S,Anderson KC,Richardson PG.Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma:a multicentre,phase 1/2,open-label,dose-escalation study.Lancet Oncol 2011;12:263-272[PMID:21345726 DOI:10.1016/S1470-2045(11)70028-6]
    141 Whitesell L,Lindquist SL.HSP90 and the chaperoning of cancer.Nat Rev Cancer 2005;5:761-772[PMID:16175177]
    142 Richardson PG,Chanan-Khan AA,Lonial S,Krishnan AY,Carroll MP,Alsina M,Albitar M,Berman D,Messina M,Anderson KC.Tanespimycin and bortezomib combination treatment in patients with relapsed or relapsed and refractory multiple myeloma:results of a phase 1/2 study.Br J Haematol 2011;153:729-740[PMID:21534941 DOI:10.1111/j.1365-2141.2011.08664.x]
    143 Di Bernardo A,Macor P,Guarnotta C,Franco G,Florena AM,Tedesco F,Tripodo C.Humoral immunotherapy of multiple myeloma:perspectives and perplexities.Expert Opin Biol Ther 2010;10:863-873[PMID:20367529 DOI:10.1517 /14712591003774063]
    144 Kumar SK,Lee JH,Lahuerta JJ,Morgan G,Richardson PG,Crowley J,Haessler J,Feather J,Hoering A,Moreau P,Le Leu X,Hulin C,Klein SK,Sonneveld P,Siegel D,BladéJ,Goldschmidt H,Jagannath S,Miguel JS,Orlowski R,Palumbo A,Sezer O,Rajkumar SV,Durie BG.Risk of progression and survival in multiple myeloma relapsing after therapy with IMi Ds and bortezomib:a multicenter international myeloma working group study.Leukemia 2012;26:149-157[PMID:21799510 DOI:10.1038/leu.2011.196]
    145 Lozanski G,Heerema NA,Flinn IW,Smith L,Harbison J,Webb J,Moran M,Lucas M,Lin T,Hackbarth ML,Proffitt JH,Lucas D,Grever MR,Byrd JC.Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53mutations and deletions.Blood 2004;103:3278-3281[PMID:14726385]
    146 BladéJ,de Larrea CF,Rosiol L.Incorporating monoclonal antibodies into the therapy of multiple myeloma.J Clin Oncol 2012;30:1904-1906[PMID:22291081 DOI:10.1200/JCO.2011.40.4178]
    147 Richardson PG,Lonial S,Jakubowiak AJ,Harousseau JL,Anderson KC.Monoclonal antibodies in the treatment of multiple myeloma.Br J Haematol 2011 Jul 21;Epub ahead of print[PMID:21777223 DOI:10.1111/j.1365-2141.2011.08790.x]
    148 Lambert JM.Drug-conjugated antibodies for the treatment of cancer.Br J Clin Pharmacol 2013;76:248-262[PMID:23173552 DOI:10.1111/bcp.12044]

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