European perspective on multiple myeloma treatment strategies in 2014

Oncologist

Volumn 19, Issue 8, 2014, Pages 829-844

  Ludwig, Heinz ^a   Sonneveld, Pieter ^b   Davies, Faith ^c   Bladé, Joan ^d   Boccadoro, Mario ^e   Cavo, Michele ^f   Morgan, Gareth ^g   de la Rubia, Javier ^h   Delforge, Michel ⁱ   Dimopoulos, Meletios ^j   Einsele, Hermann ^k   Facon, Thierry ^l   Goldschmidt, Hartmut ^m   Moreau, Philippe ⁿ   Nahi, Hareth ^o   Plesner, Torben ^p   San Miguel, Jesús ^q   Hajek, Roman ^r   Sondergeld, Pia ^s   Palumbo, Antonio ^e  

^a WILHELMINEN HOSPITAL   (Austria)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^d INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^e MOLINETTE HOSPITAL   (Italy)

^f Institute of Hematology and Medical Oncology   (Italy)

^g ROYAL MARSDEN HOSPITAL   (United Kingdom)

^h HOSPITAL UNIVERSITARIO LA FE   (Spain)

ⁱ UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^j UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^k UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^l LILLE UNIVERSITY HOSPITAL   (France)

^m UNIVERSITY OF HEIDELBERG   (Germany)

ⁿ NANTES UNIVERSITY HOSPITAL   (France)

^o KAROLINSKA INSTITUTE   (Sweden)

^p UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^q UNIVERSITY OF NAVARRA   (Spain)

^r UNIVERSITY OF OSTRAVA   (Czech Republic)

^s JUSTUS LIEBIG UNIVERSITY   (Germany)

more..

Author keywords

Autologous stem cell transplantation; Consolidation; Elderly patients; Maintenance; Multiple myeloma; Nontransplant setting; Risk stratification

Indexed keywords

ANTHRACYCLINE; ANTINEOPLASTIC AGENT; ARRY 520; BORTEZOMIB; CARFILZOMIB; CYCLODEPSIPEPTIDE; CYCLOPHOSPHAMIDE; DEHYDRODIDEMNIN B; DEXAMETHASONE; DOXORUBICIN; ELOTUZUMAB; GRANULOCYTE COLONY STIMULATING FACTOR; IXAZOMIB; LENALIDOMIDE; MELPHALAN; OPROZOMIB; PANOBINOSTAT; POMALIDOMIDE; PREDNISONE; QUISINOSTAT; RICOLINOSTAT; SALINOSPORAMIDE A; THALIDOMIDE; UNCLASSIFIED DRUG; VINCRISTINE;

ALLOGENEIC STEM CELL TRANSPLANTATION; ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; CANCER THERAPY; CLINICAL ASSESSMENT; HUMAN; MAINTENANCE CHEMOTHERAPY; META ANALYSIS (TOPIC); MINIMAL RESIDUAL DISEASE; MULTIPLE MYELOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RELAPSE; RISK FACTOR; SYSTEMATIC REVIEW (TOPIC); TREATMENT OUTCOME; AGED; AUTOTRANSPLANTATION; DISEASE FREE SURVIVAL; EUROPE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; PATHOLOGY;

AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DEXAMETHASONE; DISEASE-FREE SURVIVAL; EUROPE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; MULTIPLE MYELOMA; TRANSPLANTATION, AUTOLOGOUS; TREATMENT OUTCOME;

EID: 84905494130     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2014-0042     Document Type: Article

References (142)

1. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008; 111: 2521-2526.
2. Kumar SK, Rajkumar SV, Dispenzieri A et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516-2520.
3. Kumar SK, Dispenzieri A, Lacy MQ et al. Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia 2013; 28.
4. Turesson I, Velez R, Kristinsson SY et al. Patterns of improved survival in patients with multiple myeloma in the twenty-first century: A populationbased study. J Clin Oncol 2010; 28: 830-834.
5. Venner CP, Connors JM, Sutherland HJ et al. Novel agents improve survival of transplant patients with multiple myeloma including those with highrisk disease defined by early relapse (, 12 months). Leuk Lymphoma 2011; 52: 34-41.
6. Anderson KC, Alsina M, Bensinger W et al. Multiple myeloma, version 1.2013. J Natl Compr Canc Netw 2013; 11: 11-17.
7. Moreau P, San Miguel J, Ludwig H et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(suppl 6): vi133-vi137.
8. Engelhardt M, Terpos E, Kleber M et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica 2014; 99: 232-242.
9. Oxford Centre for Evidence-Based Medicine. Levels of Evidence (March 2009). Available at http: //www. cebm. net/oxford-centre-evidencebased-medicine-levels-evidence-march-2009/. Accessed July 18, 2014.
10. Moreau P, Cavo M, Sonneveld P et al. Combination of International Scoring System 3, high lactate dehydrogenase, and t(4; 14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progressionrelated death. J Clin Oncol 2014 [Epub ahead of print].
11. Mikhael JR, Dingli D, Roy V et al. Management of newly diagnosed symptomatic multiple myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc 2013; 88: 360-376.
12. Chng WJ, Dispenzieri A, Chim CS et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 2014; 28: 269-277.
13. Cavo M, Salwender H, Rosinol L et al. Double vs. single autologous stem cell transplantation after bortezomib-based induction regimens for multiple myeloma: An integrated analysis of patient-level data from phase European III studies. Blood 2013; 122: 767a.
14. San Miguel J, Weisel K, Moreau P et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): A randomised, open-label, phase 3 trial. Lancet Oncol 2013; 14: 1055-66.
15. Leleu X, Karlin L, Macro M et al. Pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma (RRMM) with deletion (del)17p and/or translocation t(4; 14). Blood 2013; 122: 689a.
16. Chapman MA, Lawrence MS, Keats JJ et al. Initial genome sequencing and analysis of multiple myeloma. Nature 2011; 471: 467-472.
17. Johnson SK, Heuck CJ, Albino AP et al. The use of molecular-based risk stratification and pharmacogenomics for outcome prediction and personalized therapeutic management of multiple myeloma. Int J Hematol 2011; 94: 321-333.
18. Morgan G, Johnsen HE, Goldschmidt H et al. MyelomA Genetics International Consortium. Leuk Lymphoma 2012; 53: 796-800.
19. Kaiser MF, Johnson DC, Wu P et al. Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma. Blood 2013; 122: 219-226.
20. Costa LJ, Zhang MJ, Zhong X et al. Trends in utilization and outcomes of autologous transplantation as early therapy for multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 1615-1624.
21. Cavo M, Tacchetti P, Patriarca F et al. 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.
22. Harousseau JL, Attal M, Avet-Loiseau H et al. 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 3 trial. J Clin Oncol 2010; 28: 4621-4629.
23. Rosiñol L, Oriol A, Teruel AI et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: A randomized phase 3 PETHEMA/ GEM study. Blood 2012; 120: 1589-1596.
24. Sonneveld P, Schmidt-Wolf IG, van der Holt B et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: Results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol 2012; 30: 2946-2955.
25. Sonneveld P, Goldschmidt H, Rosiñol L et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: A meta-analysis of phase III randomized, controlled trials. J Clin Oncol 2013; 31: 3279-3287.
26. Nooka AK, Kaufman JL, Behera M et al. Bortezomib-containing induction regimens in transplant-eligible myeloma patients: A metaanalysis of phase 3 randomized clinical trials. Cancer 2013; 119: 4119-4128.
27. Moreau P, Pylypenko H, Grosicki S et al. 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.
28. Blanes M, Lahuerta JJ, González JD et al. Intravenous busulfan and melphalan as a conditioning regimen for autologous stemcell transplantation in patients with newly diagnosed multiple myeloma: A matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant 2013; 19: 69-74.
29. Reece D, Song K, LeBlanc R et al. Efficacy and safety of busulfan-based conditioning regimens for multiplemyeloma. The Oncologist2013; 18: 611-618.
30. Roussel M, Moreau P, Huynh A et al. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: A phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 2010; 115: 32-37.
31. Doo NW, Thompson PA, Prince HM et al. Bortezomib with high dose melphalan conditioning for autologous transplant is safe and effective in patients with heavily pretreated and high risk multiple myeloma. Leuk Lymphoma 2013; 54: 1465-1472.
32. Miyamoto T, Yoshimoto G, Kamimura T et al. Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma. Int J Hematol 2013; 98: 337-345.
33. Cavo M, Pantani L, Petrucci MT et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood 2012; 120: 9-19.
34. Cavo M, Galli M, Pezzi A et al. Persistent improvement in clinical outcomes with bortezomibthalidomide-dexamethasone vs. thalidomidedexamethasoneincorporatedintodoubleautologous transplantation for multiple myeloma: An updated analysis of Phase 3 Gimema-MMY-3006 study. Blood 2013; 122: 2090a.
35. Morgan GJ, Davies FE, Gregory WM et al. Longterm follow-up of MRC Myeloma IX trial: Survival outcomeswith bisphosphonate and thalidomide treatment. Clin Cancer Res 2013; 19: 6030-6038.
36. Kalff A, Kennedy N, Smiley A et al. Thalidomide consolidation post autologous stem cell transplant (ASCT) for multiple myeloma (MM) is cost-effective with durable survival benefit at 5 years post randomisation: Final analysis of the ALLG MM6 study. Blood 2013; 122: 537a.
37. Attal M, Lauwers-Cances V, Marit G et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma: Follow-up analysis of the IFM 2005-02 trial. Blood 2013; 122: 406a.
38. McCarthy P, Owzar K, Hofmeister C et al. Analysis of overall survival (OS) in the context of cross-over from placebo to lenalidomide and the incidence of second primary malignancies (SPM) in the phase III study of lenalidomide versus placebo maintenance therapy following autologous stem cell transplant (ASCT) for multiple myeloma (MM) CALGB (ALLIANCE) ECOG BMTCTN 100104. Clin Lymphoma Myeloma Leuk 2013; 13(suppl 1): S15-5a.
39. Gay F, Cavallo F, Caravita T et al. Maintenance therapy with lenalidomide significantly improved survival of young newly diagnosed multiple myeloma patients. Blood 2013; 122: 2089a.
40. Palumbo A, Cavallo F, Hardan I et al. 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 2011; 118: 3069a.
41. Palumbo A, Hajek R, Delforge M et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012; 366: 1759-1769.
42. Palumbo A, Bringhen S, Rajkumar V et al. Second primary malignancies (SPM) in newly diagnosed myeloma (MM) patients treated with lenalidomide (Len): Meta-analysis of 6, 383 individual patient data (IPD). J Clin Oncol 2013; 31(suppl): 8517a.
43. Rosinol L, Oriol A, Teruel AI et al. Maintenance therapy after stem-cell transplantation for multiple myeloma with bortezomib/thalidomide vs. thalidomide vs. alfa2b-interferon: Final results of a phase III pethema/GEM randomized trial. Blood 2012; 120: 334a.
44. Sonneveld P, Scheid C, van der Holt B et al. Bortezomib induction and maintenance treatment iImproves survival in patients with newly diagnosed multiple myeloma: Extended follow-up of the HOVON-65/GMMG-HD4 trial. Blood 2013; 122: 404a.
45. Burnette BL, Dispenzieri A, Kumar S et al. Treatment trade-offs in myeloma: A survey of consecutive patients about contemporary maintenance strategies. Cancer 2013; 119: 4308-4315.
46. Jordan K, Proskorovsky I, Lewis P et al. Effect of general symptom level, specific adverse events, treatment patterns, and patient characteristics on health-related quality of life in patients with multiple myeloma: Results of a European, multicenter cohort study. Support Care Cancer 2013 [Epub ahead of print].
47. Naumann-Winter F, Greb A, Borchmann P et al. First-line tandem high-dose chemotherapy and autologous stem cell transplantation versus single high-dose chemotherapy and autologous stem cell transplantation in multiple myeloma, a systematic review of controlled studies. Cochrane Database Syst Rev 2012; 10: CD004626.
48. Kumar SK, Lacy MQ, Dispenzieri A et al. Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer 2012; 118: 1585-1592.
49. Cook G, Liakopoulou E, Pearce R et al. Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: A study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 2011; 17: 1638-1645.
50. Jimenez-Zepeda VH, Mikhael J, Winter A et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: Impact on progression-free and overall survival. Biol Blood Marrow Transplant 2012; 18: 773-779.
51. Lemieux E, Hulin C, Caillot D et al. Autologous stem cell transplantation: An effective salvage therapy in multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 445-449.
52. Michaelis LC, Saad A, Zhong X et al. Salvage second hematopoietic cell transplantation in myeloma. Biol Blood Marrow Transplant 2013; 19: 760-766.
53. Gonsalves WI, Gertz MA, Lacy MQet al. Second auto-SCT for treatment of relapsed multiple myeloma. Bone Marrow Transplant 2013; 48: 568-573.
54. Sellner L, Heiss C, Benner A et al. Autologous retransplantation for patients with recurrent multiple myeloma: A single-center experience with 200 patients. Cancer 2013; 119: 2438-2446.
55. Cook G, Williams C, Brown JM et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): A randomised, open-label, phase 3 trial. Lancet Oncol. 2014 [Epub ahead of print].
56. Lokhorst H, Einsele H, Vesole D et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol 2010; 28: 4521-4530.
57. Bruno B, Rotta M, Patriarca F et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007; 356: 1110-1120.
58. Giaccone L, Storer B, Patriarca F et al. Longterm follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma. Blood 2011; 117: 6721-6727.
59. Björkstrand B, Iacobelli S, Hegenbart U et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: Longterm follow-up. J Clin Oncol 2011; 29: 3016-3022.
60. Garban F, Attal M, Michallet M et al. 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.
61. Moreau P, Garban F, Attal M et al. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood 2008; 112: 3914-3915.
62. Rosiñol L, Pérez-Simón JA, Sureda A et al. 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: 3591-3593.
63. Krishnan A, Pasquini MC, Logan B et al. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): A phase 3 biological assignment trial. Lancet Oncol 2011; 12: 1195-1203.
64. Lokhorst HM, van der Holt B, Cornelissen JJ et al. Donor versus no-donor comparison of newly diagnosed myeloma patients included in the HOVON-50 multiple myeloma study. Blood 2012; 119: 6219-6225; quiz 6399.
65. Gahrton G, Iacobelli S, Björkstrand B et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs. autologous transplantation in multiple myeloma: Long-term results of the EBMTNMAM2000 study. Blood 2013; 121: 5055-5063.
66. Kharfan-Dabaja MA, Hamadani M, Reljic T et al. Comparative efficacy of tandem autologous versus autologous followed by allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. J Hematol Oncol 2013; 6: 2.
67. Freytes CO, Vesole DH, LeRademacher J et al. Second transplants for multiple myeloma relapsing after a previous autotransplant-reduced-intensity allogeneic vs. autologous transplantation. Bone Marrow Transplant 2014; 49: 416-421.
68. Einsele H, Liebisch P, Hebart H et al. Allogeneic stem cell transplantation for high-risk multiple myeloma. Haematologica 2011; 96(suppl 1): S11.
69. Kröger N, Badbaran A, Zabelina T et al. Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 398-404.
70. El-Cheikh J, Crocchiolo R, Furst S et al. Lenalidomide plus donor-lymphocytes infusion after allogeneic stem-cell transplantation with reduced-intensity conditioning in patients with high-risk multiple myeloma. Exp Hematol 2012; 40: 521-527.
71. Caballero-Velázquez T, López-Corral L, Encinas C et al. Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post-allogeneic transplantation for high-risk myeloma patients. Br J Haematol 2013; 162: 474-482.
72. Munshi NC, Anderson KC. Minimal residual disease in multiple myeloma. J Clin Oncol 2013; 31: 2523-2526.
73. Korthals M, Sehnke N, Kronenwett R et al. Molecular monitoring of minimal residual disease in the peripheral blood of patients with multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 1109-1115.
74. Martinez-Lopez J, Fernández-Redondo E, García-Sánz R et al. Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/ PETHEMA study. Br J Haematol 2013; 163: 581-589.
75. Martinez-Lopez J, Garcia-Sanz R, Pepin F et al. Prognostic value of deep sequencing method for minimal residual disease (MRD) detection in multiple myeloma. J Clin Oncol 2013; 31(suppl): 8511a.
76. Paiva B, Vidriales MB, Cerveró J et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood 2008; 112: 4017-4023.
77. Paiva B, Martinez-Lopez J, Vidriales MB et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol 2011; 29: 1627-1633.
78. Paiva B, Gutiérrez NC, Rosiñol L et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood 2012; 119: 687-691.
79. Puig N, Sarasquete ME, Balanzategui A et al. Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry. Leukemia 2014; 28: 391-397.
80. Rawstron AC, Child JA, de Tute RM et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: Impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol 2013; 31: 2540-2547.
81. Zamagni E, Patriarca F, Nanni C et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood 2011; 118: 5989-5995.
82. Palumbo A, Bringhen S, Ludwig H et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: A report of the European Myeloma Network (EMN). Blood 2011; 118: 4519-4529.
83. Palumbo A, Mina R. Management of older adults with multiple myeloma. Blood Rev 2013; 27: 133-142.
84. Palumbo A, Rajkumar SV, San Miguel JF et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 2014; 32: 587-600.
85. Guglielmelli T, Palumbo A. Incorporating novel agents in the management of elderly myeloma patients. Curr Hematol Malig Rep 2013; 8: 261-269.
86. Ludwig H, Avet-Loiseau H, Bladé J et al. European perspective on multiple myeloma treatment strategies: Update following recent congresses. The Oncologist2012; 17: 592-606.
87. Niesvizky R, Flinn I, Rifkin RM et al. Efficacy and safety of three bortezomib-based induction and maintenance regimens in previously untreated, transplant-ineligible multiple myeloma (MM) patients (Pts): Final results from the randomized, phase 3b, US community-based UPFRONT study (NCT00507416). Blood 2013; 122: 1966a.
88. Larocca A, Cavallo F, Magarotto V et al. Reduced dose-intensity subcutaneous bortezomib plus prednisone (VP) or plus cyclophosfamide (VCP) or plus melphalan (VMP) for newly diagnosed multiple myeloma patients older than 75 years of age. Blood 2013; 122: 539a.
89. Ludwig H, Adam Z, Hajek R et al. Light chaininduced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: Results of a phase II study. J Clin Oncol 2010; 28: 4635-4641.
90. Scheid C, Sonneveld P, Schmidt-Wolf IG et al. 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.
91. Delforge M, Terpos E, Richardson PG et al. Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma. Eur J Haematol 2011; 86: 372-384.
92. Palumbo A, Magarotto V, Bringhen S et al. A randomized phase 3 trial of melphalanlenalidomide-prednisone(MPR) or cyclophosphamideprednisone-lenalidomide (CPR) vs. lenalidomide plus dexamethsone (Rd) in elderly newly diagnosed multiple myeloma patients. Blood 2013; 122: 536a.
93. Benboubker L, Dimopoulos MA, Dispenzieri A et al. Lenalidomide and dexamethasone in transplant-ineligible myeloma patients. NEJM (in press).
94. Mateos MV, Oriol A, Martínez-López J et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood 2012; 120: 2581-2588.
95. Morgan GJ, Gregory WM, Davies FE et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and metaanalysis. Blood 2012; 119: 7-15.
96. Palumbo A, Bringhen S, Larocca A et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: Updated follow-up and improved survival. J Clin Oncol 2014; 32: 634-640.
97. Ludwig H, Bolejack V, Crowley J et al. Survival and years of life lost in different age cohorts of patients with multiple myeloma. J Clin Oncol 2010; 28: 1599-1605.
98. Nigam Y, Knight J, Bhattacharya S et al. Physiological changes associated with aging and immobility. J Aging Res 2012; 2012: 468469.
99. Bataille R, Annweiler C, Beauchet O. Multiple myeloma international staging system: "Staging" or simply "aging" system? Clin Lymphoma Myeloma Leuk 2013; 13: 635-637.
100. Gay F, Larocca A, Wijermans P et al. Complete response correlates with long-term progressionfree and overall survival in elderly myeloma treated with novel agents: Analysis of 1175 patients. Blood 2011; 117: 3025-3031.
101. Bringhen S, Mateos MV, Zweegman S et al. Age and organ damage correlate with poor survival in myeloma patients: Meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica 2013; 98: 980-987.
102. Kleber M, Ihorst G, Gross B et al. Validation of the Freiburg Comorbidity Index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome. Clin Lymphoma Myeloma Leuk 2013; 13: 541-551.
103. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011; 364: 1046-1060.
104. Palumbo A. Tailoring multiple myeloma therapy for special populations. Clin Lymphoma Myeloma Leuk 2013; 13(suppl 1): S1-4a.
105. Larocca A, Bringhen S, Evangelista A et al. A simple score, based on geriatric assessment, improves prediction of survival, and risk of serious adverse events in elderly newly diagnosed multiple myeloma patients. Blood 2013; 122: 687a.
106. Dispenzieri A, Stewart AK, Chanan-Khan A et al. Smoldering multiple myeloma requiring treatment: Time for a new definition? Blood 2013; 122: 4172-4181.
107. Tageja N, Manasanch EE, Korde N et al. Smoldering multiple myeloma: Present position and potential promises. Eur J Haematol 2014; 92: 1-12.
108. Mateos MV, Hernández MT, Giraldo P et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 2013; 369: 438-447.
109. Dhodapkar MV, Sexton R, Waheed S et al. Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120). Blood 2014; 123: 78-85.
110. Fernández de Larrea C, Jiménez R, Rosiñol L et al. Pattern of relapse and progression after autologous SCT as upfront treatment for multiple myeloma. Bone Marrow Transplant 2014; 49: 223-227.
111. Knopf KB, Duh MS, Lafeuille MH et al. Metaanalysis of the efficacy and safety of bortezomib retreatment in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk 2013; 13(suppl 1): P-228a.
112. Dimopoulos MA, Petrucci MT, Foa R et al. Analysis of second-line lenalidomide following initial relapse in the MM-015 Trial. Blood 2012; 120: 944a.
113. Laubach JP, Mitsiades CS, Mahindra A et al. Management of relapsed and relapsed/refractory multiple myeloma. J Natl Compr Canc Netw 2011; 9: 1209-1216.
114. Lonial S, Mitsiades CS, Richardson PG. Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res 2011; 17: 1264-1277.
115. Jakubowiak A. Management strategies for relapsed/refractory multiple myeloma: Current clinical perspectives. Semin Hematol 2012; 49(suppl 1): S16-S32.
116. RichardsonPG, Xie W, Jagannath S et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood 2014; 123: 1461-1469.
117. Ludwig H, Kasparu H, Leitgeb C et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 2014; 123: 985-991.
118. Jakubowiak AJ, Dytfeld D, Griffith KA et al. 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.
119. Lawasut P, Chauhan D, Laubach J et al. New proteasome inhibitors in myeloma. Curr Hematol Malig Rep 2012; 7: 258-266.
120. Moreau P. The future of therapy for relapsed/ refractory multiple myeloma: Emerging agents and novel treatment strategies. Semin Hematol 2012; 49 (suppl 1): S33-S46.
121. Moreau P, Richardson PG, Cavo M et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood 2012; 120: 947-959.
122. San Miguel J, Weisel K, Moreau P et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): A randomised, open-label, phase 3 trial. Lancet Oncol 2013; 14: 1055-1066.
123. Wang M, Martin T, Bensinger W et al. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood 2013; 122: 3122-3128.
124. Siegel DS, Martin T, Wang M et al. 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.
125. Richardson PG, Hofmeister CC, Rosenbaum CA et al. Twice-weekly oral MLN9708 (ixazomib citrate), an investigational proteasome inhibitor, in combination with lenalidomide (Len) and dexamethasone (Dex) in patients (Pts) with newly diagnosed multiple myeloma (MM): Final phase 1 results and phase 2 data. Blood 2013; 122: 535a.
126. Tai YT, Anderson KC. Antibody-based therapies in multiple myeloma. Bone Marrow Res 2011; 2011: 924058.
127. Lonial S, Kaufman J, Laubach J et al. Elotuzumab: A novel anti-CS1 monoclonal antibody for the treatment of multiple myeloma. Expert Opin Biol Ther 2013; 13: 1731-1740.
128. Lonial S, Vij R, Harousseau JL et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 2012; 30: 1953-1959.
129. Richardson PG, Jagannath S, Moreau P et al. Phase 2 study of elotuzumab plus lenalidomide/ dexamethasone (Len/Dex) in relapsed/refractory multiple myeloma (RR MM). Clin Lymphoma Myeloma Leuk 2013; 13(suppl 1): S145a.
130. Plesner T, Lokhorst H, Gimsing P et al. Daratumumab, a CD38 monoclonal antibody in patients with multiple myeloma (MM): Data from a dose-escalation phase I/II study. Clin Lymphoma Myeloma Leuk 2013; 13(suppl 1): P-130a.
131. Martin TG, Strickland SA, Glenn M et al. SAR650984, a CD38 monoclonal antibody in patients with selected CD381hematological malignancies-Data from a dose-escalation phase I study. Blood 2013; 122: 284a.
132. Endell J, Boxhammer R, Wurzenberger C et al. The activity of MOR202, a fully human anti-CD38 antibody, is complemented by ADCP and is synergistically enhanced by lenalidomidein vitro and in vivo. Blood 2012; 120: 4018a.
133. Witt O, Deubzer HE, Milde T et al. HDAC family: What arethe cancer relevant targets? Cancer Lett 2009; 277: 8-21.
134. Richardson PG, Mitsiades CS, Laubach JP et al. Preclinical data and early clinical experience supporting the use of histone deacetylase inhibitors in multiple myeloma. Leuk Res 2013; 37: 829-837.
135. Dimopoulos M, Siegel DS, Lonial S et al. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): A multicentre, randomised, double-blind study. Lancet Oncol 2013; 14: 1129-1140.
136. San Miguel J, Hungria VT, Yoon SS et al. Randomized, double blind, placebo-controlled phase 3 study of panobinostat or placebo with bortezomi and dexamethasone in relapsed and relapsed and refractory multiple myeloma (Panorama I). EHA 2014: 3347a.
137. Minami J, Suzuki R, Mazitschek R et al. Histone deacetylase 3 as a novel therapeutic target in multiple myeloma. Leukemia 2014; 28: 680-689.
138. Lonial S, Shah JJ, Zonder J et al. Prolonged survival and improved response rates with ARRY-520 in relapsed/refractory multiple myeloma (RRMM) patients with low a-1 acid glycoprotein (AAG) levels: Results from a phase 2 study. Blood 2013; 122: 285a.
139. Mateos MV, Cibeira MT, Richardson PG et al. Phase II clinical and pharmacokinetic study of plitidepsin 3-hour infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma. Clin Cancer Res 2010; 16: 3260-3269.
140. Fassas A, Shaughnessy J, Barlogie B. Cure of myeloma: Hype or reality? Bone Marrow Transplant 2005; 35: 215-224.
141. Barlogie B, Shaughnessy JD Jr. Genomics and cure in multiple myeloma: Oral presentation at IMW 2011 during session on "High-risk entities of myeloma: From biology to treatment". Haematologica 2011; 96(suppl 1): S10.
142. San-Miguel JF, Mateos MV. Can multiple myeloma become a curable disease? Haematologica 2011; 96: 1246-1248.