Outcome and toxicity in the modern era of new drugs for multiple myeloma: A reappraisal for comparison with future investigational trials

Clinical Lymphoma, Myeloma and Leukemia

Volumn 10, Issue 5, 2010, Pages 353-360

  Offidani, Massimo ^a   Leoni, Pietro ^a   Corvatta, Laura ^a   Polloni, Claudia ^a   Gentili, Silvia ^a   Liberati, Anna Marina ^b   Pulini, Stefano ^c   Gozzetti, Alessandro ^d   Ballanti, Stelvio ^b   Nozzoli, Chiara ^e   Palumbo, Antonio ^f  

^a OSPEDALI RIUNITI   (Italy)

^b UNIVERSITY OF PERUGIA   (Italy)

^c SPIRITO SANTO HOSPITAL   (Italy)

^d UNIVERSITY HOSPITAL OF SIENA   (Italy)

^e CAREGGI UNIVERSITY HOSPITAL   (Italy)

^f UNIVERSITY OF TURIN   (Italy)

Author keywords

Alkylating Agents; Anthracyclines; Bortezomib; Lenalidomide; Thalidomide

Indexed keywords

BORTEZOMIB; CLARITHROMYCIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DOXORUBICIN; LENALIDOMIDE; MELPHALAN; PREDNISONE; THALIDOMIDE; VINCRISTINE; ANTINEOPLASTIC AGENT; BORONIC ACID DERIVATIVE; DRUG DERIVATIVE; PYRAZINE DERIVATIVE;

BLOOD TOXICITY; CANCER COMBINATION CHEMOTHERAPY; CLINICAL PROTOCOL; CLINICAL TRIAL; CUMULATIVE MAIN NONHEMATOLOGIC TOXICITY; DRUG ACTIVITY; DRUG EFFICACY; DRUG SAFETY; DRUG SCREENING; DRUG TOXICITY; HUMAN; MULTIPLE MYELOMA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; REVIEW; SURVIVAL RATE; TREATMENT RESPONSE; DISEASE FREE SURVIVAL; TREATMENT OUTCOME;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORONIC ACIDS; DISEASE-FREE SURVIVAL; HUMANS; MULTIPLE MYELOMA; PYRAZINES; THALIDOMIDE; TREATMENT OUTCOME;

EID: 79952278406     PISSN: 21522650     EISSN: 21522669     Source Type: Journal    
DOI: 10.3816/CLML.2010.n.068     Document Type: Review

References (68)

1. Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6 633 patients from 27 randomized trials. J Clin Oncol 1998; 16:3832-42.
2. Barlogie B, Schaughnessy J, Tricot G, et al. Treatment of multiple myeloma. Blood 2004; 103:20-32. (Pubitemid 38029914)
3. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335:91-7. (Pubitemid 26240110)
4. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348:1875-83. (Pubitemid 36532313)
5. Hideshima T, Mitsiades C, Tonon G, et al. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer 2007; 7:585-98. (Pubitemid 47106630)
6. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341:1565-71.
7. D'Amato RJ, Lentzsch S, Anderson KC, et al. Mechanism of action of thalidomide and 3-aminoothalidomide in multiple myeloma. Semin Oncol 2001; 28:597-601. (Pubitemid 33134418)
8. Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivates as anticancer agents. Nat Rev Cancer 2004; 4:314-22. (Pubitemid 38525287)
9. Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 2004; 4:349-60. (Pubitemid 38579481)
10. Rajkumar SV, Richardson PG, Hideshima T, et al. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 2005; 23:630-9. (Pubitemid 46224241)
11. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348:2609-17. (Pubitemid 36741588)
12. Dingli D, Rajkumar SV, Nowakowski GS, et al. Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing upfront autologous stem cell transplantation: a phase II trial. Haematologica 2005; 90:1650-4. (Pubitemid 41814989)
13. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129:776-83. (Pubitemid 40904528)
14. Cavo M, Zamagni E, Tosi P, et al. Superiority of thalidomide and dexamethasone over vincristine- doxorubicin dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005; 106:35-9. (Pubitemid 40967171)
15. Wu P, Davies FE, Horton C, et al. The combination of cyclophosphamide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide-vincristine-doxorubicin-methylprednisolone as induction chemotherapy prior to autologous transplantation of multiple myeloma: a case matched analysis. Leuk Lymphoma 2006; 47:2335-8. (Pubitemid 44768426)
16. Offidani M, Corvatta L, Piersantelli MN, et al. Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood 2006; 108:2159-64. (Pubitemid 44497495)
17. Hussein MA, Baz R, Srkalovic G, et al. Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma. Mayo Clin Proc 2006; 81:889-95. (Pubitemid 43993480)
18. Mateos MV, Hernández JM, Hernández MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006; 108:2165-72.
19. 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. Presented at: the 48th American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2006; Orlando, FL. Abstract 57.
20. Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354:1021-30. (Pubitemid 43357806)
21. Lacy MQ, Gertz MA, Dispenzieri A, et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc 2007; 82:1179-84. (Pubitemid 47502875)
22. Wang M, Giralt S, Delasalle K, et al. Bortezomib in combination with thalidomide-dexamethasone for previously untreated multiple myeloma. Hematology 2007; 12:235-9. (Pubitemid 46930250)
23. Rosinol L, Oriol A, Mateos M, et al. Final results of a phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen prior autologous stem cell transplantation (ASCT) in younger patients with multiple myeloma (MM): efficacy and clinical implications of tumor response. J Clin Oncol 2007; 25(18 suppl):447s (abstract 8024).
24. Jakubowiak AJ, Al-Zoubi A, Kendall T, et al. Combination therapy with bortezomib (VELCADE), Doxil and dexamethasone (VDD) in newly diagnosed myeloma: updated results of phase II clinical trial. Haematologica 2007; 92:180-1.
25. Belch A, Reece DE, Bahlis NJ, et al. Bortezomib (VELCADE), pegylated liposomal doxorubicin (DOXIL/CAELYX) and dexamethasone in the treatment of previously untreated multiple myeloma patients: impact on quality-of-life. Presented at: the 49th American Society of Hematology (ASH) Annual Meeting and Exposition; December 8-11, 2007; Atlanta GA. Abstract 3618.
26. 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; 25:4459-65. (Pubitemid 350063804)
27. Zonder JA, Crowley J, Hussein MA, et al. Superiority of lenalidomide (Len) plus high-dose dexamethasone (HD) compared to HD alone as treatment of newly-diagnosed multiple myeloma (NDMM): results of the randomized, double-blinded, placebo-controlled SWOG Trial S0232. Presented at: the 49th American Society of Hematology (ASH) Annual Meeting and Exposition; December 8-11, 2007; Atlanta, GA. Abstract 77.
28. Zervas K, Mihou D, Katodritou E, et al. VAD-Doxil versus VAD-Doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek myeloma study group. Ann Oncol 2007; 18:1369-75. (Pubitemid 47305012)
29. Facon T, Mary J, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma. Lancet 2007; 370:1209-18. (Pubitemid 47516593)
30. Palumbo A, Bringhen S, Caravita T, et al. 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. (Pubitemid 43363369)
31. Popat R, Oakervee HE, Hallam S, et al. Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up. Br J Haematol 2008; 141:512-6. (Pubitemid 351550543)
32. Reeder CB, Stewart AK, Hentz JG, et al. Efficacy of induction with CyBorD in newly diagnosed multiple myeloma. J Clin Oncol 2008; 26(15 suppl):458s (abstract 8517).
33. Kumar S, Flinn IW, Nogan SJ, et al. Safety and efficacy of novel combination therapy with bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in newly diagnosed multiple myeloma: initial results from the phase I/II multicenter EVOLUTION study. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 93.
34. Bensinger W, Jagannath S, Vescio R, et al. A phase II study of bortezomib (Velcade), cyclophosphamide (Cytoxan), thalidomide (Thalomid) and dexamethasone as first-line therapy for multiple myeloma. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 94.
35. Kumar S, Hayman S, Buadi F, et al. Phase II trial of lenalidomide (Revlimid) with cyclophosphamide and dexamethasone (RCd) for newly diagnosed myeloma. Blood 2008; 112:40 (abstract 91).
36. Rosinol L, Cibeira MT, Martinez J, et al. Thalidomide/dexamethasone (TD) vs. bortezomib (Velcade/Thalidomide/Dexamethasone (VTD) vs. VBMCP/VBAD/Velcade as induction regimens prior autologous stem cell transplantation (ASCT) in younger patients with multiple myeloma (MM): first results of a prospective phase III PETHEMA/Gem Trial. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 654.
37. 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. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 92.
38. 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-nave symptomatic multiple myeloma. Blood 2008; 111:1101-9. (Pubitemid 351213388)
39. Mateos M-V, Oriol A, Martinez J, et al. Bortezomib (Velcade)-Melphalan- Prednisone (VMP) versus Velcade-Thalidomide-Prednisone (VTP) in elderly untreated multiple myeloma patients: which is the best partner for velcade: an alkylating or an immunomodulator agent? Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 651.
40. Knop S, Liebisch P, Wandt H, et al. Bortezomib, intravenous cyclophosphamide and dexamethasone (VelCD) for previously untreated multiple myeloma: an interim analysis of the German DSMM XIa Trial. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 2776.
41. Palumbo A, Falco P, Gay F, et al. Bortezomib-doxorubicin-dexamethasone as induction prior to reduced intensity autologous transplantation followed by lenalidomide as consolidation/maintenance in elderly untreated myeloma patients. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 159.
42. 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). Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 653.
43. Wijeramans 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. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 649.
44. Palumbo A, Bringhen S, Rossi D, et al. A prospective, randomized, phase III study of bortezomib, melphalan prednisone and thalidomide (VMPT) versus bortezomib, melphalan and prednisone (VMP) in elderly newly diagnosed myeloma patients. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 652.
45. Gulbrandsen N, Waage A, Gimsing P, et al. A randomized placebo controlled study with melphalan/prednisone vs. melphalan/prednisone/thalidomide: quality of life and toxicity. Haematologica (EHA Annual Meeting Abstracts) 2008; 93: (abstract 0209).
46. Rajkumar SV, Jacobus S, Callander N, et al. Randomized trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed myeloma (E4A03), a trial coordinated by the Eastern Cooperative Oncology Group: analysis of response, survival, and outcome. J Clin Oncol 2008; 26(15 suppl):445s (abstract 8504).
47. Cavo M, Tacchetti P, Patriarca F, et al. Superior complete response rate and progression-free survival after autologous transplantation with up-front velcade-thalidomide-dexamethasone compared with thalidomide-dexamethasone in newly diagnosed multiple myeloma. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 158.
48. Rajkumar SV, Rosinl 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; 26:2171-7.
49. 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. J Clin Oncol 2008; 26(15 suppl):458s (abstract 8505).
50. Lokhorst HL, van der Holt B, Zweegman S, et al. Final analysis of HOVON-50 randomized phase III study on the effect of thalidomide combined with adriamycin, dexamethasone (AD) and high dose melphalan (HDM) in patients with multiple myeloma (MM). Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 157.
51. Pineda-Roman M, Zangari M, Haessler J, et al. Sustained complete remission in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Br J Haematol 2008; 140:625-34. (Pubitemid 351300910)
52. 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; 359:906-17.
53. Ludwig H, Hajek R, Tóthova E, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009; 113:3435-42.
54. 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; 27:3664-70.
55. Kropff M, Liebisch P, Knop S, et al. DSMM IX study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma. Ann Hematol 2009; 88:1125-30.
56. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111:2516-20.
57. Ocio EM, Mateos MV, Maiso P, et al. New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings. Lancet Oncol 2008; 9:1157-65.
58. Mitsiades CS, Hideshima T, Chauhan D, et al. Emerging treatments of multiple myeloma; beyond IMIDs and bortezomib. Semin Hematol 2009; 46:166-75.
59. Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and hemopoietic stem cell transplantation. Br J Haematol 1998; 102:1115-23. (Pubitemid 28435189)
60. Wang M, Delasalle K, Thomas S, et al. Complete remission represents the major surrogate marker of long survival in multiple myeloma. Presented at: the 48th American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2006; Orlando, FL. Abstract 403.
61. van de Velde HJ, Liu X, Chen G, et al. Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica 2007; 92:1399-406. (Pubitemid 350144158)
62. Lahuerta JJ, Mateos MV, Martínez-López J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol 2008; 26:5775-82.
63. Cavo M, Tacchetti P, Patriarca F, et al. Superior complete response rate and progression-free survival after autologous transplantation with up-front velcade-thalidomide-dexamethasone compared with thalidomide-dexamethasone in newly diagnosed multiple myeloma. Presented at: the 50th American Society of Hematology (ASH) Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 158.
64. Kumar SK, Dingli D, Dispenzieri A, et al. Impact of additional cytoreduction following autologous SCT in multiple myeloma. Bone Marrow Transplant 2008; 42:259-64.
65. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22:414-23. (Pubitemid 351255436)
66. Palumbo A, Cavo M, Bringhen S, et al. A phase III study of enoxaparin vs. aspirin vs. low-dose warfarin as thromboprophylaxis for newly diagnosed myeloma patients treated with thalidomide based-regimens. Presented at: the 51st American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2009; New Orleans, LA. Abstract 492.
67. Richardson PG, Mitsiades C, Schlossman R, et al. New drugs for myeloma. Oncologist 2007; 12:664-89. (Pubitemid 47036203)
68. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 2008; 112:1593-9