Improving induction therapy in multiple myeloma

Current Hematologic Malignancy Reports

Volumn 5, Issue 3, 2010, Pages 119-128

  Nooka, Ajay ^a   Gleason, Charise ^a   Lonial, Sagar ^a  

^a EMORY UNIVERSITY   (United States)

Author keywords

Bortezomib; IMiDs; MRD Combination therapy; Myeloma; Novel agents; Proteasome inhibitors; Transplant eligible; Transplant ineligible

Indexed keywords

ALPHA2B INTERFERON; BORTEZOMIB; CLARITHROMYCIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DOXORUBICIN; GRANULOCYTE COLONY STIMULATING FACTOR; IMMUNOMODULATING AGENT; LENALIDOMIDE; MELPHALAN; PREDNISOLONE; PREDNISONE; PROTEASOME INHIBITOR; THALIDOMIDE; VINCRISTINE;

ALKYLATION; ANEMIA; CANCER REGRESSION; DEEP VEIN THROMBOSIS; DRUG MEGADOSE; HUMAN; IMMUNOMODULATION; LEUKOPENIA; LOW DRUG DOSE; LUNG EMBOLISM; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYOPATHY; NEUTROPENIA; PATIENT SELECTION; PERIPHERAL NEUROPATHY; RASH; REVIEW; STEM CELL TRANSPLANTATION; THROMBOCYTOPENIA; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; IMMUNOLOGIC FACTORS; MULTIPLE MYELOMA; PROTEASE INHIBITORS; STEM CELL TRANSPLANTATION; SURVIVAL RATE;

EID: 77955981073     PISSN: 15588211     EISSN: 1558822X     Source Type: Journal    
DOI: 10.1007/s11899-010-0057-7     Document Type: Review

References (42)

1. Kumar SK, Rajkumar SV, Dispenzieri A, et al.: Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008, 111:2516-2520.
2. Harousseau JL, Mathiot C, Attal M, et al.: Bortezomib/dexamethasone versus VAD as induction prior to autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM): Updated data from IFM 2005/01 trial [abstract]. J Clin Oncol (Meeting Abstracts) 2008, 26:8505.
3. Harousseau J-L, Avet-Loiseau H, Attal M, et al.: High complete and very good partial response rates with bortezomibdexamethasone as induction prior to ASCT in newly diagnosed patients with high-risk myeloma: results of the IFM2005-01 Phase Trial [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:353.
4. Rajkumar SV, Jacobus S, Callander NS, et al.: 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(1):29-37. This study established the noninferiority and minimal toxicity of low-dose dexamethasone in combination with lenalidomide compared with high-dose dexamethasone in combination with lenalidomide.
5. Cavo M, Tacchetti P, Patriarca F, et al.: A phase III study of double autotransplantation incorporating bortezomib-thalidomidedexamethasone (VTD) or thalidomide-dexamethasone (TD) for multiple myeloma: superior clinical outcomes with VTD compared to TD [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:351.
6. Harousseau J-L, Avet-Loiseau H, Facon T, et al.: Bortezomib plus dexamethasone (VD) versus reduced-dose bortezomib plus thalidomide plus dexamethasone (vTD) as induction treatment prior to autologous stem-cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM) [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:354. This study demonstrated that bortezomib administered at a lower dose (1.0 mg/m2) in addition to thalidomide and dexamethasone (vTD arm) induced better response rates and reduced the incidence of PN significantly compared with bortezomib administered at 1.3 mg/m2 and dexamethasone (VD arm).
7. Niesvizky R, Jayabalan DS, Christos PJ, et al.: BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood 2008, 111:1101-1109.
8. Richardson P, Lonial S, Jakubowiak A, et al.: Lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed multiple myeloma: encouraging efficacy in high risk groups with updated results of a phase I/II study [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:92.
9. Palumbo A, Cavallo F, Yehuda DB, et al.: A prospective, randomized study of melphalan, prednisone, lenalidomide (MPR) versus melphalan (200 mg/m2) and autologous transplantation (Mel200) in newly diagnosed myeloma patients: an interim analysis [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:350.
10. Jakubowiak AJ, Hofmeister CC, Campagnaro EL, et al.: Lenalidomide, bortezomib, pegylated liposomal doxorubicin hydrochloride, and dexamethasone in newly diagnosed multiple myeloma: initial results of phase I/II MMRC trial [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:132.
11. Kumar S, Flinn IW, Hari PN, et al.: Novel three- and four-drug combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for newly diagnosed multiple myeloma: encouraging results from the multi-center, randomized, phase 2 EVOLUTION study [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:127.
12. Reeder CB, Reece DE, Kukreti V, et al.: Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 2009, 23:1337-1341.
13. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group. J Clin Oncol 1998, 16:3832-3842.
14. San Miguel JF, Schlag R, Khuageva NK, et al.: Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008, 359:906-917. This pivotal study proved that achieving IFx-negative CRs could be possible without having to undergo transplantation. It reported 33% IFx-negative CRs in the VMP arm and only 4% IFx-negative CRs in the MP arm.
15. Mateos MV, Richardson PG, Schlag R, et al.: Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated followup and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 2010 Apr 19 (Epub ahead of print).
16. Attal M, Harousseau J-L, Stoppa A-M, et al.: A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 1996, 335:91-97.
17. Kristinsson SY, Landgren O, Rajkumar VS: Novel therapies in multiple myeloma for newly diagnosed nontransplant candidates. Cancer J 2009, 15:473-478.
18. Badros A, Barlogie B, Siegel E, et al.: Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001, 114:822-829.
19. Rajkumar SV, Rosinol L, Hussein M, et al.: 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, 26:2171-2177.
20. Ludwig H, Hajek R, Tothova E, et al.: Thalidomidedexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009, 113:3435-3442.
21. Popat R, Goff L, Oaekervee HE, et al.: Changes in Mcl-1 and Bim expression with bortezomib and melphalan therapy for multiple myeloma [abstract]. Blood (ASH Annual Meeting Abstracts) 2005, 106:2481.
22. Facon T, Mary JY, Hulin C, et al.: Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reducedintensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): A randomised trial. Lancet 2007, 370:1209-1218.
23. Hulin C, Facon T, Rodon P, et al.: 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, 27:3664-3670.
24. W0ijermans P, Schaafsma M, van Norden Y, et al.: Melphalan + prednisone versus melphalan + prednisone + thalidomide in induction therapy for multiple myeloma in elderly patients: final analysis of the Dutch cooperative group HOVON 49 study [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:649.
25. Palumbo A, Bringhen S, Liberati AM, et al.: Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 2008, 112:3107-3114.
26. Gulbrandsen N, Waage A, Gimsing P, et al.: A randomized placebo controlled study with melphalan/prednisone versus melphalan/prednisone/ thalidomide: quality of life and toxicity [abstract 0209]. European Hematology Association 13th Congress. Copenhagen, Denmark; 13 June 2008.
27. Kapoor P, Rajkumar SV, Dispenzieri A, et al.: Melphalan and prednisone (MP) versus melphalan, prednisone and thalidomide (MPT) as initial therapy for previously untreated elderly and/or transplant ineligible patients with multiple myeloma: A metaanalysis of randomized controlled trials [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:615.
28. Mateos M-V, Oriol A, Martinez J, et al.: A prospective, multicenter, randomized, trial of bortezomib/melphalan/prednisone (VMP) versus bortezomib/thalidomide/prednisone (VTP) as induction therapy followed by maintenance treatment with bortezomib/thalidomide (VT) versus bortezomib/prednisone (VP) in elderly untreated patients with multiple myeloma older than 65 years [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:3. This phase 3 trial induced an IFx-neg immunophenotypic CR rate of 23% and 22% in the two bortezomib-containing induction regimens.
29. Palumbo A, Falco P, Corradini P, et al.: Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: A report from the GIMEMA Italian Multiple Myeloma Network. J Clin Oncol 2007, 25:4459-4465.
30. Palumbo A, Falco P, Falcone A, et al.: Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. Clin Lymphoma Myeloma 2009, 9:145-150.
31. Palumbo A, Dimopoulos MA, Delforge M, et al.: A phase III study to determine the efficacy and safety of lenalidomide in combination with melphalan and prednisone (MPR) in elderly patients with newly diagnosed multiple myeloma [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:613.
32. Palumbo A, Bringhen S, Rossi D, et al.: Bortezomib, melphalan, prednisone and thalidomide (VMPT) followed by maintenance with bortezomib and thalidomide for initial treatment of elderly multiple myeloma patients [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:128. This trial reported that bortezomib can be safely administered as a weekly infusion without losing efficacy, minimizing PN.
33. Corradini P, Voena C, Tarella C, et al.: Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells. J Clin Oncol 1999, 17:208-215.
34. Martinelli G, Terragna C, Zamagni E, et al.: Polymerase chain reaction-based detection of minimal residual disease in multiple myeloma patients receiving allogeneic stem cell transplantation. Haematologica 2000, 85:930-934.
35. Palumbo A, Cavallo F, Pagliano G, et al.: Early consolidation with bortezomib, thalidomide and dexamethasone in MM patients in CR or VGPR following autologous transplantation induces molecular remissions [abstract 0190]. European Hematology Association 13th Congress. Copenhagen, Denmark; 13 June 2008.
36. Harousseau J,Mathiot C, Attal M, et al.: Bortezomib/dexamethasone versus VAD as induction prior to autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM): Updated data from IFM 2005/01 trial [abstract]. J Clin Oncol 2008, 26:8505.
37. Macro M, Divine M, Uzunhan Y, et al.: Dexamethasone + thalidomide (Dex/Thal) compared to VAD as a pre-transplant treatment in newly diagnosed multiple myeloma (MM): A randomized trial [abstract]. Blood (ASH Annual Meeting Abstracts) 2006, 108:57.
38. Cavo M, Bringhen S, Testoni N, et al.: Clinical outcomes according to genomic abnormalities in 566 newly diagnosed multiple myeloma patients treated with bortezomib-based regimens [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:1868.
39. Morgan GJ, Davies FE, Gregory WM, et al.: 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 [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:352.
40. Lokhorst HM, Schmidt-Wolf I, Sonneveld P, et al.: Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica 2008, 93:124-127.
41. Sonneveld P, van der Holt B, Schmidt-Wolf IGH, et al.: First analysis of HOVON-65/GMMG-HD4 randomized phase III trial comparing bortezomib, Adriamycin, dexamethasone (PAD) vs VAD as induction treatment prior to high dose melphalan (HDM) in patients with newly diagnosed multiple myeloma (MM) [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:653.
42. Facon T, Mary JY, Pegourie B, et al.: Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood 2006, 107:1292-1298.