1,192
Views
11
CrossRef citations to date
0
Altmetric
Reviews

Emerging biological insights and novel treatment strategies in multiple myeloma

, , &
Pages 407-438 | Published online: 27 Aug 2012

Bibliography

  • Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860-73
  • Kyle RA, Gertz MA, Witzig TE, Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33
  • Landgren O, Kyle RA, Pfeiffer RM, Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009;113:5412-17
  • Weiss BM, Abadie J, Verma P, A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009;113:5418-22
  • Blade J, Rosinol L, Cibeira MT. Are all myelomas preceded by MGUS? Blood 2009;113:5370
  • Jemal A, Siegel R, Xu J, Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300
  • Kristinsson SY, Landgren O, Dickman PW, Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol 2007;25:1993-9
  • Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008;111:2521-6
  • Kumar SK, Rajkumar SV, Dispenzieri A, Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516-20
  • Raab MS, Podar K, Breitkreutz I, Multiple myeloma. Lancet 2009;374:324-39
  • Kumar SK, Lee JH, Lahuerta JJ, Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia 2012;26:149-57
  • Durie BG, Kyle RA, Belch A, Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2003;4:379-98
  • Terpos E, Moulopoulos LA, Dimopoulos MA. Advances in imaging and the management of myeloma bone disease. J Clin Oncol 2011;29:1907-15
  • Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-57
  • Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36:842-54
  • Greipp PR, San Miguel J, Durie BG, International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20
  • Snozek CL, Katzmann JA, Kyle RA, Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008;22:1933-7
  • Jakob C, Sterz J, Liebisch P, Incorporation of the bone marker carboxy-terminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma. Leukemia 2008;22:1767-72
  • Durie BG. The role of anatomic and functional staging in myeloma: description of Durie/Salmon plus staging system. Eur J Cancer 2006;42:1539-43
  • Avet-Loiseau H, Attal M, Moreau P, Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 2007;109:3489-95
  • Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2:175-87
  • Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol 2005;23:6333-8
  • Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011;364:1046-60
  • Anderson KC. Oncogenomics to target myeloma in the bone marrow microenvironment. Clin Cancer Res 2011;17:1225-33
  • Roodman GD. Pathogenesis of myeloma bone disease. Leukemia 2009;23:435-41
  • Hideshima T, Mitsiades C, Tonon G, Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer 2007;7:585-98
  • Carrasco DR, Tonon G, Huang Y, High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell 2006;9:313-25
  • Avet-Loiseau H, Li C, Magrangeas F, Prognostic significance of copy-number alterations in multiple myeloma. J Clin Oncol 2009;27:4585-90
  • Davies FE, Dring AM, Li C, Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood 2003;102:4504-11
  • Zhan F, Hardin J, Kordsmeier B, Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood 2002;99:1745-57
  • Magrangeas F, Nasser V, Avet-Loiseau H, Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease. Blood 2003;101:4998-5006
  • Broyl A, Hose D, Lokhorst H, Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood 2010;116:2543–53
  • Shaughnessy JD Jr, Zhan F, Burington BE, A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood 2007;109:2276-84
  • Decaux O, Lode L, Magrangeas F, Intergroupe Francophone du Myelome. 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 Myelome. J Clin Oncol 2008;26:4798-805
  • Pichiorri F, Suh SS, Ladetto M, MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA 2008;105(35):12885-90
  • Gertz MA, Lacy MQ, Dispenzieri A, 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;106:2837-40
  • Gutierrez NC, Castellanos MV, Martin ML, Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia 2007;21:143-50
  • Kapoor P, Kumar S, Fonseca R, Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood 2009;114:518-21
  • Fonseca R, Bergsagel PL, Drach J, International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009;23:2210-21
  • Rajkumar SV, Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 2005;80:1371-82
  • Facon T, Mary JY, Harousseau JL, Front-line or rescue autologous bone marrow transplantation (ABMT) following a first course of high dose melphalan (HDM) in multiple myeloma (MM). Preliminary results of a prospective randomized trial (CIAM) protocol. Blood (ASH annual meeting abstracts) 1996;88(Suppl 1):685a
  • Fermand JP, Ravaud P, Chevret S, High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 1998;92:3131-6
  • Kumar SK, Mikhael JR, Buadi FK, Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc 2009;84:1095-110
  • Blade J, Dimopoulos M, Rosinol L, Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J Clin Oncol 2010;28:690-7
  • Kyle RA, Remstein ED, Therneau TM, Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007;356:2582-90
  • Kyle RA, Durie BG, Rajkumar SV, Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010;24:1121-7
  • Stewart AK, Richardson PG, San-Miguel JF. How I treat multiple myeloma in younger patients. Blood 2009;114:5436-43
  • Palumbo A, Bringhen S, Petrucci MT, Intermediate dose melphalan improves survival of myeloma patients aged 50–70: results of a randomized controlled trial. Blood 2004;104:3052-7
  • Facon T, Mary JY, Hulin C, 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. Lancet 2007;370:1209-18
  • Palumbo A, Sezer O, Kyle R, International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. Leukemia 2009;23:1716-30
  • Mateos MV, Oriol A, Martinez-Lopez J, 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;11:934-41
  • Garban F, Attal M, Michallet M, 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;107:3474-80
  • Rosinol L, Perez-Simon JA, Sureda A, A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 2008;112:3591-3
  • Bruno B, Rotta M, Patriarca F, Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood 2009;113:3375-82
  • Morabito F, Gentile M, Mazzone C, Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugs. Eur J Haematol 2010;85:181-91
  • Rajkumar SV, Rosinol L, Hussein M, Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008;26:2171-7
  • Rajkumar SV, Jacobus S, Callander NS, 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
  • Harousseau JL, Attal M, Avet-Loiseau H, Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010;28:4621-9
  • Sonneveld P, Schmidt-Wolf I, van der Holt B, HOVON-65/GMMGHD4 randomized phase III trial comparing bortezomib, doxorubicin, dexamethasone (PAD) vs VAD followed by high-dose melphalan (HDM) and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma (MM). Blood (ASH annual meeting abstracts) 2010;116:23
  • Reeder CB, Reece DE, Kukreti V, Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 2009;23:1337-41
  • Cavo M, Tacchetti P, Patriarca F, 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;376:2075-85
  • Richardson PG, Weller E, Lonial S, Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010;116:679-86
  • Harousseau JL, Avet-Loiseau H, Mary J, Bortezomib plus dexamethasone versus reduced-dose bortezomib plus thalidomide-dexamethasone as induction prior to autologous transplantation in newly diagnosed myeloma. Haematologica (EHA annual meeting abstracts) 2010;95(Suppl 2):451
  • Rosiñol L, Cibeira MT, Mateos MV, A phase III PETHEMA/GEM study of induction therapy prior autologous stem cell transplantation (ASCT) in multiple myeloma: superiority of VTD (bortezomib/thalidomide/dexamethasone) over TD and VBMCP/VBAD plus bortezomib. Blood (ASH annual meeting abstracts) 2010;116:139
  • Moreau P, Avet-Loiseau H, Facon T, 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;118:5752-8
  • Kumar SK, Flinn I, Noga SJ, Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia 2010;24:1350-6
  • Kumar S, Flinn I, Richardson PG, Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 2012;119:4375-82
  • Ludwig H, Viterbo L, Greil R, Phase II study of bortezomib, thalidomide and dexamethasone/-cyclophosphamide as induction therapy in previously untreated multiple myeloma (MM): safety and activity including evaluation of MRD. Haematologica (EHA annual meeting abstracts) 2010;95(Suppl 2):149-50
  • Barlogie B, Anaissie E, van Rhee F, Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007;138:176-85
  • van Rhee F, Szymonifka J, Anaissie E, Total therapy 3 for multiple myeloma: prognostic implications of cumulative dosing and premature discontinuation of VTD maintenance components, bortezomib, thalidomide, and dexamethasone, relevant to all phases of therapy. Blood 2010;116:1220-7
  • Nair B, van Rhee F, Shaughnessy JD Jr, 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;115:4168-73
  • Attal M, Harousseau JL, Facon T, Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003;349:2495-502
  • Cavo M, Tosi P, Zamagni E, Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: bologna 96 clinical study. J Clin Oncol 2007;25:2434-41
  • Palumbo A, Cavallo F, Hardan I, Melphalan/Prednisone/Lenalidomide (MPR) Versus High-Dose Melphalan and Autologous Transplantation (MEL200) in Newly Diagnosed Multiple Myeloma (MM) Patients < 65 Years: Results of a Randomized Phase III Study. Blood (ASH annual meeting abstracts) 2011;118:3069
  • Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 (IFM/DFCI2009). Available from: http://www.clinicaltrials.gov/ct2/show/NCT01208662?term_nct01208662&rank_1 [Accessed 12 December 2011]
  • Study to compare VMP with HDM followed by VRD consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (HO95). Available from: http://www.clinicaltrials.gov/ct2/show/NCT01208766 [Accessed 12 December 2011]
  • Palumbo A, Bringhen S, Liberati AM, Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 2008;112:3107-14
  • Palumbo A, Bringhen S, Caravita T, Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006;367:825-31
  • Facon T, Mary JY, Hulin C, 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. Lancet 2007;370:1209-18
  • Wijermans P, Schaafsma M, Termorshuizen F, 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;28:3160-6
  • Hulin C, Facon T, Rodon P, Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 2009;27:3664-70
  • Waage A, Gimsing P, Fayers P, Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010;116:1405-12
  • Fayers PM, Palumbo A, Hulin C, Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 2011;118:1239-47
  • San Miguel JF, Schlag R, Khuageva NK, Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906-17
  • Mateos MV, Richardson PG, Schlag R, 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;28:2259-66
  • Palumbo A, Dimopoulos MA, Delforge M, Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012;366:1759-69
  • Palumbo A, Bringhen S, Rossi D, 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;28:5101-9
  • Palumbo A, Gay F, Falco P, Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol 2010;28:800-7
  • Attal M, Lauwers V, Marit G, Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:1782-91
  • Mellqvist UH, Westin J, Gimsing P, Improved response rate with bortezomib consolidation after high dose melphalan: first results of a Nordic Myeloma Study Group randomized phase III trial. Blood (ASH annual meeting abstracts) 2009;114:221
  • Ladetto M, Pagliano G, Ferrero S, Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 2010;28:2077-84
  • Attal M, Harousseau JL, Leyvraz S, Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006;108:3289-94
  • Spencer A, Prince HM, Roberts AW, Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009;27:1788-93
  • Cavo M, Pantani L, Petrucci MT, Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma. Blood 2012. [Epub ahead of print]
  • Morgan GJ, Davies FE, Gregory WM, The addition of thalidomide to the induction treatment of newly presenting myeloma patients increases the CR rate which is likely to translate into improved PFS and OS. Blood (ASH annual meeting abstracts) 2009;114:149
  • Stewart AK, Trudel S, Bahlis NJ, A randomized phase III trial of thalidomide and prednisone as maintenance therapy following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM): the NCIC CTG MY.10 trial. Blood (ASH annual meeting abstracts) 2010;116:23
  • Barlogie B, Anaissie E, Haessler J, Complete remission sustained 3 years from treatment initiation is a powerful surrogate for extended survival in multiple myeloma. Cancer 2008;113:355-9
  • Barlogie B, Tricot G, Anaissie E, Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006;354:1021-30
  • Lokhorst HM, van der Holt B, Zweegman S, A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood 2010;115:1113-20
  • Barlogie B, Attal M, Crowley J, Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the intergroupe francophone du myelome, southwest oncology group, and University of Arkansas for Medical Sciences. J Clin Oncol 2010;28:1209-14
  • Offidani M, Corvatta L, Polloni C, Thalidomide-dexamethasone versus interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study. Br J Haematol 2009;144:653-9
  • McCarthy PL, Owzar K, Hofmeister CC, Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366:1770-81
  • 103. Palumbo A, Adam Z, Kropff M, et al. A phase 3 study evaluating the efficacy and safety of lenalidomide (Len) combined with melphalan and prednisone followed by continuous lenalidomide maintenance (MPR-R) in patients (Pts) ≥ 65 Years (Yrs) with Newly Diagnosed Multiple Myeloma (NDMM): updated results for Pts aged 65–75 Yrs enrolled in MM-015. Blood (ASH Annual Meeting Abstracts) 2011; 118: 475.
  • National Cancer Institute. Cancer Trends Progress Report-2007 Update. Available from: http://progressreport.cancer.gov/doc_detail.asp?pid=1&did=2007&chid=75&coid=726&mid [Accessed 26 March 2008]
  • Schulman KL, Kohles J. Economic burden of metastatic bone disease in the U.S. Cancer 2007;109:2334-42
  • Ferlay J, Bray F, Sankila R, Parkin DM. EUCAN: cancer incidence, mortality and prevalence in the European Union 1998, version 5.0. IARC Cancer Base No 4. IARC Press; Lyon, France: 1999
  • Ludwig H, Bolejack V, Crowley J, Survival and years of life lost in different age cohorts of patients with multiple myeloma. J Clin Oncol 2010;28:1599-605
  • Cook R. An economic perspective on treatment options in multiple myeloma. Manag Care Oncol 2007;3:10-12
  • The NCCN Multiple Myeloma Clinical Practice Guidelines in Oncology (Version 1.2008) 2007 National Comprehensive Cancer Network, Inc. Available from: www.nccn.org [Last accessed 30 April 2102]
  • Schwartzberg L. Managed care considerations in the treatment of multiple myeloma. Manag Care Oncol 2007;3:14-16. 47
  • Fullerton DS, Hulehatt H, Huang H, A budget impact model comparing resource utilization of four approved therapies for multiple myeloma (MM) in the US. Blood (ASH annual meeting abstracts) 2007;110:3324
  • Jones JA, Qazilbash MH, Shih YC, In-hospital complications of autologous hematopoietic stem cell transplantation for lymphoid malignancies: clinical and economic outcomes from the Nationwide Inpatient Sample. Cancer 2008;112:1096-105
  • Meehan KR, Fitzmaurice T, Root L, The financial requirements and time commitments of caregivers for autologous stem cell transplant recipients. J Support Oncol 2006;4:187-90
  • Ludwig H, Beksac M, Blade J, Current multiple myeloma treatment strategies with novel agents: a European perspective. Oncologist 2010;15:6-25
  • Avet-Loiseau H, Soulier J, Fermand JP, 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;24:623-8
  • Avet-Loiseau H, Leleu X, Roussel M, Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol 2010;28:4630-4
  • Neben K, Lokhorst HM, Jauch A, Combining information regarding chromosomal aberrations t(4;14), Del(17p13) and the copy number of 1q21 with the International Staging System Classification Allows Stratification of Myeloma Patients Undergoing Autologous Stem Cell Transplantation: results from the HOVON-65/GMMG HD4 Trial. Blood (ASH Annual Meeting Abstracts) 2011;118:332
  • Kyle RA, Rajkumar SV. Treatment of multiple myeloma: a comprehensive review. Clin Lymphoma Myeloma 2009;9:278-88
  • San Miguel J, Harousseau JL, Joshua D, Anderson KC. Individualizing treatment of patients with myeloma in the era of novel agents. J Clin Oncol 2008;26:2761-6
  • Richardson PG, Jagannath S, Jakubowiak AJ, Phase II trial of lenalidomide, bortezomib, and dexamethasone in patients (pts) with relapsed and relapsed/refractory multiple myeloma (MM): updated efficacy and safety data after _2 years of follow-up. Blood (ASH annual meeting abstracts) 2010;116:1257
  • Bringhen S, Larocca A, Rossi D, Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 2010;116:4745-53
  • Moreau P, Pylypenko H, Grosicki S, Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 2011;12:431-40
  • Carrier M, Le Gal G, Tay J, Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 2011;9:653-63
  • Palumbo A, Rajkumar SV, Dimopoulos MA, Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008;22:414-23
  • Chen C, Reece DE, Siegel D, Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. Br J Haematol 2009;146:164-70
  • Stewart AK, Chang H, Trudel S, Diagnostic evaluation of t(4;14) in multiple myeloma and evidence for clonal evolution. Leukemia 2007;21:2358-9
  • Cremer FW, Bila J, Buck I, Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics. Genes Chromosomes Cancer 2005;44:194-203
  • Chng WJ, Ketterling RP, Fonseca R. Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma. Genes Chromosomes Cancer 2006;45:1111-20
  • Shaughnessy JD Jr, Qu P, Usmani S, Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3. Blood 2011;118:3512-24
  • Buda G, Ricci D, Huang CC, Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin. Ann Hematol 2010;89:1133-40
  • Nojima M, Maruyama R, Yasui H, Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma. Clin Cancer Res 2009;15:4356-64
  • Singhal S, Mehta J, Desikan R, Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341:1565-71
  • Rajkumar SV, Blood E, Vesole D, 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;24:431-6
  • Rajkumar SV, Hayman SR, Lacy MQ, Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050-3
  • Kumar S, Anderson KC. Drug insight: thalidomide as a treatment for multiple myeloma. Nat Clin Pract Oncol 2005;2:262-70
  • Richardson PG, Sonneveld P, Schuster MW, Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487-98
  • D'Amato RJ, Loughnan MS, Flynn E, Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994;91:4082-5
  • Zwingenberger K, Wnendt S. Immunomodulation by thalidomide: systematic review of the literature and of unpublished observations. J Inflamm 1995;46:177-211
  • Richardson P, Hideshima T, Anderson K. Thalidomide: emerging role in cancer medicine. Annu Rev Med 2002;53:629-57
  • Moreira AL, Sampaio EP, Zmuidzinas A, Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993;177:1675-80
  • Keifer JA, Guttridge DC, Ashburner BP, Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem 2001;276:22382-7
  • Geitz H, Handt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996;31:213-21
  • Gentile M, Recchia AG, Vigna E, Lenalidomide in the treatment of chronic lymphocytic leukemia. Expert Opin Investig Drugs 2011;20:273-86
  • Muller GW, Chen R, Huang SY, Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 1999;9:1625-30
  • Davies FE, Raje N, Hideshima T, Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98:210-16
  • Wu L, Adams M, Carter T, Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res 2008;14:4650-7
  • Teo SK. Properties of thalidomide and its analogues: implications for anticancer therapy. Aaps J 2005;7:E14-19
  • Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 2004;4:314-22
  • Hideshima T, Chauhan D, Shima Y, Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000;96:2943-50
  • Gandhi AK, Kang J, Capone L, 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;10:155-67
  • Mitsiades N, Mitsiades CS, Poulaki V, Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99:4525-30
  • Giannopoulos K, Mertens D, Stilgenbauer S. Treating chronic lymphocytic leukemia with thalidomide and lenalidomide. Expert Opin Pharmacother 2011;12(18):2857-64
  • Jung T, Catalgol B, Grune T. The proteasomal system. Mol Aspects Med 2009;30:191-296
  • Ciechanover A. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 2005;6:79-87
  • Rolfe M, Chiu MI, Pagano M. The ubiquitin-mediated proteolytic pathway as a therapeutic area. J Mol Med (Berl) 1997;75:5-17
  • Kisselev AF, Callard A, Goldberg AL. Importance of the different proteolytic sites of the proteasome and the efficacy of inhibitors varies with the protein substrate. J Biol Chem 2006;281:8582-90
  • Orlowski RZ, Eswara JR, Lafond-Walker A, Tumor growth inhibition induced in a murine model of human Burkitt's lymphoma by a proteasome inhibitor. Cancer Res 1998;58:4342-8
  • Shinohara K, Tomioka M, Nakano H, Apoptosis induction resulting from proteasome inhibition. Biochem J 1996;317(Pt 2):385-8
  • Wilkinson KD. Ubiquitination and deubiquitination: targeting of proteins for degradation by the proteasome. Semin Cell Dev Biol 2000;11:141-8
  • Dorsey BD, Iqbal M, Chatterjee S, Discovery of a potent, selective, and orally active proteasome inhibitor for the treatment of cancer. J Med Chem 2008;51:1068-72
  • Groll M, Ditzel L, Lowe J, Structure of 20S proteasome from yeast at 2.4 A resolution. Nature 1997;386:463-71
  • Kopp F, Hendil KB, Dahlmann B, Subunit arrangement in the human 20S proteasome. Proc Natl Acad Sci USA 1997;94:2939-44
  • Dick LR, Fleming PE. Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today 2010;15:243-9
  • Braun BC, Glickman M, Kraft R, The base of the proteasome regulatory particle exhibits chaperone-like activity. Nat Cell Biol 1999;1:221-6
  • Orlowski M, Wilk S. Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. Arch Biochem Biophys 2000;383:1-16
  • Hideshima T, Ikeda H, Chauhan D, Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood 2009;114:1046-52
  • James DF, Betty MR, Mosadeghi R, Kipps TJ. Lenalidomide abrogates the protective influence of nurse-like cells on primary chronic lymphocytic leukemia cells in vitro. Blood (ASH annual meeting abstracts) 2007;110:3116
  • Mukherjee S, Raje N, Schoonmaker JA, Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest 2008;118:491-504
  • Breitkreutz I, Raab MS, Vallet S, Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia 2008;22:1925-32
  • Lentzsch S, LeBlanc R, Podar K, Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia 2003;17:41-4
  • Gorgun G, Calabrese E, Soydan E, Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 2010;116:3227-37
  • Xu Y, Li J, Ferguson GD, Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases. Blood 2009;114:338-45
  • Ramsay AG, Johnson AJ, Lee AM, Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest 2008;118:2427-37
  • Davies FE, Raje N, Hideshima T, Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98:210-16
  • Lopez-Girona A, Mendy D, Ito T, Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia 2012; doi: 10.1038/leu.2012.119. [Epub ahead of print]
  • Ito T, Ando H, Suzuki T, Identification of a primary target of thalidomide teratogenicity. Science 2010;327:1345-50
  • Fulciniti M, Tassone P, Hideshima T, Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 2009;114:371-9
  • Chauhan D, Singh AV, Brahmandam M, Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell 2009;16:309-23
  • Prabhala RH, Neri P, Bae JE, Dysfunctional T regulatory cells in multiple myeloma. Blood 2006;107:301-4
  • Prabhala RH, Pelluru D, Fulciniti M, Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010;115:5385-92
  • Hideshima T, Mitsiades C, Akiyama M, Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003;101:1530-4
  • Vallet S, Mukherjee S, Vaghela N, Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci USA 2010;107:5124-9
  • Kuhn DJ, Chen Q, Voorhees PM, Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood 2007;110:3281-90
  • Bennett MK, Kirk CJ. Development of proteasome inhibitors in oncology and autoimmune diseases. Curr Opin Drug Discov Devel 2008;11:616-25
  • Parlati F, Lee SJ, Aujay M, Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. Blood 2009;114:3439-47
  • Vij R, Wang M, Kaufman JL, An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood 2012. [Epub ahead of print]
  • Vij R, Siegel DS, Kaufman JL, Results of an ongoing open-label, phase II study of carfilzomib in patients with relapsed and/or refractory multiple myeloma (R/R MM) [abstract 8000]. J Clin Oncol 2010;28(15s):573s
  • Singhal S, Siegel DS, Martin T, Integrated safety from phase 2 studies of monotherapy carfilzomib in patients with relapsed and refractory multiple myeloma (MM): an updated analysis [abstract 1876]. Blood 2011;118(21):819
  • Jakubowiak AJ, Martin T, Singhal S, Responses to. single-agent carfilzomib (CFZ) are not affected by cytogenetics in patients (pts) with relapsed and refractory multiple myeloma (R/R MM) [abstract 117]. Ann Oncol 2011;22(Suppl 4):iv122
  • Lonial S, Baz RC, Wang M, Phase I study of twice-weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients (pts) with relapsed and/or refractory multiple myeloma (MM). 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):8017
  • Jakubowiak AJ, Dytfeld D, Griffith KA, A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 2012. [Epub ahead of print]
  • Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma, US National Library of Medicine. 2011. Available from: http://clinicaltrials.gov/ct2/show/NCT01080391 [Last accessed 30 April 2012]
  • Sonneveld P, Hacker E, Zweegman S, Carfilzomib combined with thalidomide and dexamethasone (CARTHADEX) as induction treatment prior to high-dose melphalan (HDM) in newly diagnosed patients with multiple myeloma (MM) [abstract 633]. A trial of the European Myeloma Network EMN. Blood 2011;118(21):290
  • Mikhael J, Reeder CB, Libby EN, A phase I/II trial of cyclophosphamide, carfilzomib, thalidomide, and dexamethasone (CYCLONE) in patients with newly diagnosed multiple myeloma. 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):8010
  • Jakubowiak AJ, Dytfeld D, Jagannath S, Final results of a frontline phase 1/2 study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in multiple myeloma (MM) [abstract 631]. Blood 2011;118(12):288-9
  • Korde N, Zingone A, Kwok M, Phase II clinical and correlative study of carfilzomib, lenalidomide, and dexamethasone (CRd) in newly diagnosed multiple myeloma (MM) patients. 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):e18568
  • Chauhan D, Singh AV, Aujay M, A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 2010;116:4906-15
  • Berdeja JG, Richardson PG, Lonial S, Phase 1/2 study of oral MLN9708, a novel, investigational proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma (MM) [abstract 479]. Blood 2011;118(21):223
  • Kumar S, Bensinger WI, Reeder CB, Weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients (pts) with relapsed/refractory multiple myeloma (MM): a phase I study. 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):803
  • Chauhan D, Singh AV, Ciccarelli B, Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma. Blood 2010;115:834-45
  • Richardson PG, Spencer A, Cannell P, Phase 1 clinical evaluation of twice-weekly Marizomib (NPI–0052), a novel proteasome inhibitor, in patients with relapsed/refractory multiple myeloma (MM). Blood (ASH annual meeting abstracts) 2011;118:302
  • Chauhan D, Catley L, Li G, A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 2005;8:407-19
  • Chauhan D, Tian Z, Nicholson B, Deubiquitylating enzyme USP 7, a novel therapeutic target in multiple myeloma. Blood (ASH annual meeting abstracts) 2009;114:610
  • Singh AV, Bandi M, Aujay MA, PR-924, a selective inhibitor of the immunoproteasome subunit LMP-7, blocks multiple myeloma cell growth both in vitro and in vivo. Br J Haematol 2011;152:155-63
  • Kuhn DJ, Hunsucker SA, Chen Q, Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors. Blood 2009;113:4667-76
  • Hideshima T, Bradner JE, Wong J, Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci USA 2005;102:8567-72
  • Catley L, Weisberg E, Kiziltepe T, Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood 2006;108:3441-9
  • Mitsiades CS, Mitsiades NS, McMullan CJ, Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci USA 2004;101:540-5
  • David E, Schafer-Hales K, Marcus AI, Combination of bortezomib with tipifarnib (R115777) induces synergistic myeloma cell apoptosis via down-regulation of HDAC6 and inhibition of aggresome formation. Blood (ASH annual meeting abstracts) 2007;110:1520
  • Weber DM, Jagannath S, Sobecks R, Vorinostat plus bortezomib in MM: a phase I study. Clin Lymphoma Myeloma (XII International Myeloma Workshop Abstract Book) 2009;9(S44):A248
  • Weber DM, Badros A, Jagannath S, Vorinostat and bortezomib in relapsed/refractory MM. Clin Lymphoma Myeloma (XII International Myeloma Workshop Abstract Book) 2009;9(S42):A242
  • Jagannath S, Weber D, Sobecks R, The combination of vorinostat and bortezomib provides long-term responses in patients with relapsed or refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts) 2009;114:3886
  • Siegel D, Dimopoulos MA, Yoon SS, Vantage 095: vorinostat in combination with bortezomib in salvage multiple myeloma patients: final study results of a global phase 2b trial. Blood (ASH Annual Meeting Abstracts) 2011;118:480
  • Dimopoulos MA, Jagannath S, Yoon SS, Vantage 088: vorinostat in combination with bortezomib in patients with relapsed/refractory multiple myeloma: results of a global, randomized phase 3 trial. Blood (ASH Annual Meeting Abstracts) 2011;118:811
  • San Miguel J, Sezer O, Siegel D, A phase IB dose-escalation study of oral panobinostat (LBH589) and IV bortezomib in patients with relapsed or relapsed and refractory multiple myeloma. Haematologica (EHA annual meeting abstracts) 2010;95(Suppl 2):155:0384
  • San-Miguel J, de Moraes Hungria VT, Yoon SS, Update on a Phase III Study of Panobinostat with Bortezomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: PANORAMA 1. Blood (ASH Annual Meeting Abstracts) 2011;118:3976
  • Alsina M, Schlossman RL, Weber DM, PANORAMA 2: a phase II study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma. 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):8012
  • Richter JR, Bilotti E, McBride L, Salvage therapy with vorinostat, lenalidomide, and dexamethasone (ZRD) in lenalidomide/dexamethasone relapsed/refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts) 2011;118:3986
  • Santo L, Hideshima T, Kung AL, Selective inhibition of HDAC6 with a new prototype inhibitor (ACY–1215) overcomes bortezomib resistance in multiple myeloma (MM). Blood (ASH annual meeting abstracts) 2010;116:2997
  • McMillin DW, Hunter Z, Delmore J, MLN4924, a novel investigational NEDD8 activating enzyme inhibitor, exhibits preclinical activity in multiple myeloma and Waldenstrom's macroglobulinemia through mechanism distinct from existing proteasome inhibitors. Blood (ASH annual meeting abstracts) 2010;116:2988
  • Streetly MJ, Gyertson K, Daniel Y, Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol 2008;141:41-51
  • Schey SA, Fields P, Bartlett JB, Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004;22:3269-76
  • Galustian C, Meyer B, Labarthe MC, The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother 2009;58:1033-45
  • Verhelle D, Corral LG, Wong K, Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res 2007;67:746-55
  • Shalapour S, Zelmer A, Pfau M, The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest in childhood acute lymphoblastic leukemia cells in vitro and in vivo. Clin Cancer Res 2006;12:5526-32
  • Lacy MQ, Hayman SR, Gertz MA, Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 2009;27:5008-14
  • Lacy MQ, Allred JB, Gertz MA, Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 2011;118:2970-5
  • Leleu X, Attal M, Moreau P, High response rates to pomalidomide and dexamethasone in patients with refractory myeloma, final analysis of IFM 2009-02. Blood (ASH Annual Meeting Abstracts) 2011;118:812
  • Santo L, Vallet S, Hideshima T, AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene 2010;29:2325-36
  • Raje N, Kumar S, Hideshima T, Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Blood 2004;104:4188-93
  • Ghobrial IM, Weller E, Vij R, 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;12:263-72
  • Mahindra A, Richardson PG, Hari P, Updated results of a phase I study of RAD001 in combination with lenalidomide in patients with relapsed or refractory multiple myeloma with pharmacodynamic and pharmacokinetic analysis. Blood (ASH annual meeting abstracts) 2010;116:3051
  • Mitsiades CS, Mitsiades NS, McMullan CJ, Antimyeloma activity of heat shock protein-90 inhibition. Blood 2006;107:1092-100
  • Patterson J, Palombella VJ, Fritz C, IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells. Cancer Chemother Pharmacol 2008;61:923-32
  • McMillin DW, Negri J, Delmore J, Activity of new heat shock protein 90 (hsp90) inhibitor NVP-AUY922 against myeloma cells sensitive and resistant to conventional agents. Blood (ASH annual meeting abstracts) 2007;110:1587
  • Seggewiss-Bernhardt R, Bargou R, Goh YT, Phase I/IB study of AUY922 alone or with Bortezomib, in patients with relapsed or refractory multiple myeloma. EHA Annual Meeting Abstracts; 2012
  • Richardson PG, Chanan-Khan AA, Alsina M, Tanespimycin monotherapy in relapsed multiple myeloma: results of a phase 1 dose-escalation study. Br J Haematol 2010;150:438-45
  • Richardson PG, Chanan-Khan AA, Lonial S, Tanespimycin + bortezomib demonstrates safety, activity, and effective target inhibition in relapsed/refractory myeloma patients: updated results of a phase 1/2 study. Blood (ASH annual meeting abstracts) 2009;114:2890
  • Richardson PG, Badros AZ, Jagannath S, Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma. Br J Haematol 2010;150:428-37
  • Usmani SZ, Chiosis G. HSP90 inhibitors as therapy for multiple myeloma. Clin Lymphoma Myeloma Leuk 2011;11(Suppl 1):S77-81
  • Chauhan D, Li G, Shringarpure R, Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. Cancer Res 2003;63:6174-7
  • Hideshima T, Podar K, Chauhan D, p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells. Oncogene 2004;23:8766-76
  • Harvey RD, Lonial S. PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma. Future Oncol 2007;3:639-47
  • Hideshima T, Catley L, Yasui H, Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood 2006;107:4053-62
  • Richardson P, Lonial S, Jakubowiak A, Multi-center phase II study of perifosine (KRX-0401) alone and in combination with dexamethasone (dex) for patients with relapsed or relapsed/refractory multiple myeloma (MM): promising activity as combination therapy with manageable toxicity. Blood (ASH annual meeting abstracts) 2007;110:1164
  • Richardson PG, Wolf J, Jakubowiak A, 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;29:4243-9
  • Jakubowiak A, Richardson P, Zimmerman T, Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study. Br J Haematol 2012. [Epub ahead of print]
  • Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients, US National Library of Medicine. 2011. Available from: http://clinicaltrials.gov/ct2/show/NCT01002248 [Last accessed 30 April 2012]
  • Morgan GJ, Davies FE, Gregory WM, First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010;376:1989-99
  • Morgan GJ, Davies FE, Gregory WM, Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial. Blood 2012;119:5374-83
  • Neri P, Kumar S, Fulciniti MT, Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model. Clin Cancer Res 2007;13:5903-9
  • Raje NS, Hohl RJ, Faber EA, Phase I study of LY2127399, a human anti-BAFF antibody, and bortezomib in patients with previously treated multiple myeloma. J Clin Oncol (ASCO annual meeting abstracts) 2011;15(Suppl):8012
  • Fulciniti M, Tassone P, Hideshima T, Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 2009;114:371-9
  • A Double-blind, Placebo-controlled, Randomized Phase 2 Study of BHQ880, an Anti-Dickkopf1 (DKK1) Monoclonal Antibody (mAb), in Patients With Untreated Multiple Myeloma and Renal Insufficiency US National Library of Medicine. 2011. Available from: http://clinicaltrials.gov/ct2/show/NCT01337752 [Last accessed 30 April 2012]
  • Vallet S, Mukherjee S, Vaghela N, Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci USA 2010;107:5124-9
  • Shinohara M, Koga T, Okamoto K, Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 2008;132:794-806
  • Tai YT, Chang BY, Kong SY, Bruton's tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma. Blood 2012. [Epub ahead of print]
  • Bam R, Pennisi A, Li X, Bruton's tyrosine kinase (BTK) is indispensable for myeloma cell migration towards SDF–1 and induction of osteoclastogenesis and osteolytic bone disease. Blood (ASH annual meeting abstracts) 2010;116:447
  • Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma US National Library of Medicine. 2011. Available from: http://clinicaltrials.gov/ct2/show/NCT01478581 [Last accessed 30 April 2012]
  • Neri P, Kumar S, Fulciniti MT, Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model. Clin Cancer Res 2007;13:5903-9
  • Tai YT, Dillon M, Song W, Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood 2008;112:1329-37
  • Zonder JA, Mohrbacher AF, Singhal S, A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood;2011. [Epub ahead of print]
  • Jakubowiak AJ, Benson DM, Bensinger W, Phase I trial of Anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/refractory multiple myeloma. J Clin Oncol 2012. [Epub ahead of print]
  • Lonial S, Vij R, Harousseau JL, Elotuzumab in combination with lenalidomide and low dose dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol 2012;30:1953-9
  • Richardson PG, Moreau P, Jakubowiak AJ, Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: interim results of a phase 2 study. Blood (ASH annual meeting abstracts) 2010;116:986
  • Dimopoulos MA, Facon T, Richardson PG, ELOQUENT-1: a phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006). 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):8113
  • Voorhees PM, Manges RF, Sonneveld P, A phase 2 multicenter study of siltuximab, an Anti-IL-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts) 2011;118:3971
  • A Phase I/IIa Study of Human Anti-CD38 Antibody MOR03087 in Relapsed/Refractory Multiple Myeloma, US National Library of Medicine. 2011. Available from: http://clinicaltrials.gov/ct2/show/NCT01421186 [Last accessed 30 April 2012]
  • Diehl V, Cheson BD. Bendamustine in the treatment of hematologic malignancies. Introduction. Semin Oncol 2002;29:1-3
  • Pönisch W, Mitrou PS, Merkle K, Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone–a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol 2006;132:205-12
  • Knop S, Straka C, Haen M, The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high dose chemotherapy. Haematologica 2005;90:1287-8
  • Pönisch W, Rozanski M, Goldschmidt H, Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a phase I clinical trial. Br J Haematol 2008;143:191-200
  • Lentzsch S, O'Sullivan A, Kennedy RC, Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 2012;119:4608-13
  • Rodon P, Hulin C, Pegourie B, Bendamustine, bortezomib, and dexamethasone (BVD) in elderly patients with relapsed/refractory multiple myeloma (RRMM): the Intergroupe Francophone du Myélome (IFM) 2009-01 protocol. 2012 ASCO Annual Meeting Proceedings. J Clin Oncol 2012;30(15 Suppl):8014
  • Offidani M, Corvatta L, Caraffa P, Bendamustine, bortezomib, and dexamethasone (BVD) combination for the treatment of relapsed/refractory multiple myeloma: an interim analysis of a phase II study. EHA; 2012
  • Chapman MA, Lawrence MS, Keats JJ, Initial genome sequencing and analysis of multiple myeloma. Nature 2011;471:467-72
  • Hadari Y, Schlessinger J. FGFR3-targeted mAb therapy for bladder cancer and multiple myeloma. J Clin Invest 2009;119:1077-9
  • Qing J, Du X, Chen Y, Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice. J Clin Invest 2009;119:1216-29
  • Martinez-Garcia E, Popovic R, Min DJ, The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood 2011;117:211-20
  • Marango J, Shimoyama M, Nishio H, The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood 2008;111:3145-54

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.