Superior overall survival of patients with myeloma achieving very good partial response or better to initial treatment with bortezomib, pegylated liposomal doxorubicin, and dexamethasone, predicted after two cycles by a free light chain- and M-protein-based model: extended follow-up of a phase II trial

References

• Cavo M, Zamagni E, Tosi P, Superiority of thalidomide and dexamethasone over vincristine-doxorubicin dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005;106:35–39.
   PubMed Web of Science ®Google Scholar
• Dimopoulos M, Spencer A, Attal M, Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007;357:2123–2132.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Schlossman RL, Weller E, Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002;100:3063–3067.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Sonneveld P, Schuster M, 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.
   PubMed Web of Science ®Google Scholar
• San Miguel JF, Schlag R, Khuageva NK, Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906–917.
   PubMed Web of Science ®Google Scholar
• Harousseau JL, Moreau P. Autologous hematopoietic stem-cell transplantation for multiple myeloma. N Engl J Med 2009;360:2645–2654.
   PubMed Web of Science ®Google Scholar
• Katzel JA, Hari P, Vesole DH. Multiple myeloma: charging toward a bright future. CA Cancer J Clin 2007;57:301–318.
   PubMed Web of Science ®Google Scholar
• Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860–1873.
   PubMed Web of Science ®Google Scholar
• 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;376:2075–2085.
   PubMed Web of Science ®Google Scholar
• Moreau P, Facon T, Attal M, Comparison of reduced-dose bortezomib plus thalidomide plus dexamethasone (vTD) to bortezomib plus dexamethasone (VD) as induction treatment prior to ASCT in de novo multiple myeloma (MM): results of IFM2007-02 study. J Clin Oncol 2010;28(15 Suppl.): Abstract 8014.
   Web of Science ®Google Scholar
• Harousseau JL, Attal M, vet-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;28:4621–4629.
   PubMed Web of Science ®Google Scholar
• Rosinol 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 2010;116(Suppl. 1): Abstract 307.
   Google Scholar
• Sonneveld P, Schmidt-Wolf I, van der Holt B, HOVON-65/GMMG-HD4 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 2010;116(Suppl. 1): Abstract 40.
   Google Scholar
• Harousseau JL, Attal M, Avet-Loiseau H. The role of complete response in multiple myeloma. Blood 2009;114: 3139–3146.
   PubMed Web of Science ®Google Scholar
• Jakubowiak AJ, Kendall T, Al-Zoubi A, 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.
   PubMed Web of Science ®Google Scholar
• van de Velde H, Liu X, Chen G, Cakana A, Deraedt W, Bayssas M. Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica 2007;92:1399–1406.
   PubMed Web of Science ®Google Scholar
• Moreau P, Attal M, Pegourie B, Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial. Blood 2010 Nov 23. [E-pub ahead of print].
   Web of Science ®Google Scholar
• Harousseau JL, Palumbo A, Richardson PG, Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood 2010;116:3743–3750.
   PubMed Web of Science ®Google Scholar
• 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;23:1337–1341.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Weller E, Lonial S, Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010;116:679–686.
   PubMed Web of Science ®Google Scholar
• Cavo M, Bringhen S, Terragna C, Bortezomib-based induction treatments improve outcomes of newly diagnosed multiple myeloma patients with high-risk cytogenetic abnormalities. Blood 2010;116(Suppl. 1): Abstract 781.
   Google Scholar
• Reece D, Song KW, Fu T, Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood 2009;114:522–525.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Barlogie B, Shaughnessy JD Jr. The molecular characterization and clinical management of multiple myeloma in the post-genome era. Leukemia 2009;23:1941–1956.
   PubMed Web of Science ®Google Scholar
• Mateos MV, Hernandez JM, Hernandez MT, Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression. Haematologica 2008;93:560–565.
   PubMed Web of Science ®Google Scholar
• Dytfeld D, Hari M, Strahler J, Proteomic profiling of multiple myeloma using iTRAQ labeling followed by multidimensional liquid chromatography and tandem mass spectrometry. Blood 2009;114(Suppl. 1): Abstract 4865.
   Google Scholar
• Hari M, MacDonald J, Friedman J, Kendall T, Mulligan G, Jakubowiak A. Gene expression profiles (GEP) to predict at least very good partial response to Velcade, Doxil, and dexamethasone in newly diagnosed patients with multiple myeloma. Blood 2007;110(Suppl. 1): Abstract 1489.
   Google Scholar
• 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;109:2276–2284.
   PubMed Web of Science ®Google Scholar
• Anaissie EJ, van Rhee F, Hoering A, Comparing toxicities and survival outcomes with Total Therapy 4 (TT4) for 70-gene (R70)-defined low-risk multiple myeloma (MM) to results obtained with Total Therapy 3 protocols TT3A and TT3B. Blood 2010;116(Suppl. 1): Abstract 368.
   PubMed Web of Science ®Google Scholar
• Orlowski R, Sutherland H, Blade J, Early normalization of serum free light chain is associated with prolonged time to progression following bortezomib ± pegylated liposomal doxorubicin treatment of relapsed/refractory multiple myeloma. Blood 2007;110(Suppl. 1): Abstract 2735.
   PubMed Web of Science ®Google Scholar
• Bradwell AR, Carr-Smith HD, Mead GP, Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001;47:673–680.
   PubMed Web of Science ®Google Scholar
• Katzmann JA, Clark RJ, Abraham RS, Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48: 1437–1444.
   PubMed Web of Science ®Google Scholar
• Durie BG, Harousseau JL, Miguel JS, International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–1473.
   PubMed Web of Science ®Google Scholar
• Kim J, Hayton WL, Robinson JM, Anderson CL. Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model. Clin Immunol 2007;122:146–155.
   PubMed Web of Science ®Google Scholar
• Dispenzieri A, Lacy MQ, Katzmann JA, Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006;107:3378–3383.
   PubMed Web of Science ®Google Scholar
• van Rhee F, Bolejack V, Hollmig K, High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 2007;110:827–832.
   PubMed Web of Science ®Google Scholar
• Blade J, Samson D, Reece D, Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998;102:1115–1123.
   PubMed Web of Science ®Google Scholar
• Friedman JF, Al-Zoubi A, Kaminski M, Kendall T, Jakubowiak A. A new model predicting at least a very good partial response in patients with multiple myeloma (MM) after 2 cycles of bortezomib-based therapy. Haematologica 2006;91(Suppl.): Abstract 0741.
   Google Scholar
• Singhal S, Vickrey E, Krishnamurthy J, Singh V, Allen S, Mehta J. The relationship between the serum free light chain assay and serum immunofixation electrophoresis, and the definition of concordant and discordant free light chain ratios. Blood 2009;114:38–39.
   PubMed Web of Science ®Google Scholar
• Kumar S, Flinn IW, Richardson PG, Novel three- and four-drug combination regimens of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for previously untreated multiple myeloma: results from the multi-center, randomized, phase 2 EVOLUTION study. Blood 2010;116(Suppl. 1): Abstract 621.
   Google Scholar
• Robson E, Mead G, Das M, Cavet J, Liakopoulou E. Free light chain analysis in patients receiving bortezomib. Haematologica 2007;92(Suppl.): Abstract PO-1019.
   PubMed Web of Science ®Google Scholar
• Dispenzieri A, Zhang L, Katzmann JA, Appraisal of immunoglobulin free light chain as a marker of response. Blood 2008;111:4908–4915.
   PubMed Web of Science ®Google Scholar
• Hajek R, Hajek R, Cernakova Z, Free light chain assays for early detection of resistance to bortezomib-based regimens. Haematologica 2007;92(Suppl.): Abstract 0257.
   Google Scholar
• Willenbacher E, Gasser S, Gastl G, Willenbacher W. Serum and urine free light chain analysis compared to conventional paraprotein measurements: usefulness for clinical decision making in real life hematology. Blood 2009;114(Suppl. 1): Abstract 2889.
   Google Scholar
• Jaskowski TD, Litwin CM, Hill HR. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis. Clin Vaccine Immunol 2006;13:277–280.
   PubMed Web of Science ®Google Scholar
• Pratt G. The evolving use of serum free light chain assays in haematology. Br J Haematol 2008;141:413–422.
   PubMed Web of Science ®Google Scholar
• Sheldon J. Free light chains. Ann Clin Biochem 2007;44:503–505.
   PubMed Web of Science ®Google Scholar
• Dispenzieri A. Is early, deep free light chain response really an adverse prognostic factor? Blood 2008;111:2490–2491.
   PubMed Web of Science ®Google Scholar
• 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;22:1933–1937.
   PubMed Web of Science ®Google Scholar
• Mead GP, Carr-Smith HD, Drayson MT, Morgan GJ, Child JA, Bradwell AR. Serum free light chains for monitoring multiple myeloma. Br J Haematol 2004;126:348–354.
   PubMed Web of Science ®Google Scholar
• 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: 1095–1110.
   PubMed Web of Science ®Google Scholar
• Nair B, van RF, 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;115:4168–4173.
   PubMed Web of Science ®Google Scholar
• Gay F, Hayman SR, Lacy MQ, Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients. Blood 2010;115:1343–1350.
   PubMed Web of Science ®Google Scholar
• Jakubowiak A, Kendall T, Al-Zoubi A, Initial treatment with bortezomib (Velcade®), Doxil®, and dexamethasone (VDD) is superior to thalidomide and dexamethasone (TD) as initial therapy prior to autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Blood 2008;112(Suppl. 1): Abstract 3713.
   PubMed Web of Science ®Google Scholar
• Jakubowiak AJ, Brackett L, Kendall T, Friedman J, Kaminski MS. Combination therapy with Velcade, Doxil, and dexamethasone (VDD) for patients with relapsed/refractory multiple myeloma (MM). Blood 2005;106(Suppl. 1): Abstract 5179.
   Google Scholar