Thalidomide in the Treatment of Multiple Myeloma: Focus on Combination with Bortezomib
Authors:
R. Hájek; H. Plonková; J. Gumulec
Authors place of work:
Klinika hematoonkologie LF OU a FN Ostrava
Published in the journal:
Klin Onkol 2013; 26(3): 163-169
Category:
Review
Summary
Thalidomide, the first clinically available immunomodulatory drug, reaches monotherapy treatment response in about 1/ 3 of significantly pretreated patients with multiple myeloma, and in combination with glucocorticoids approximately 50% response rate. After addition of conventional cytostatic into the triple combination, therapeutic response is achieved in 80% of untreated patients or about 60% of pretreated patients. Therapeutic response is achieved even in 1/3 of patients with refractory multiple myeloma resistant to other available treatment. With regard to the frequency of adverse effects, particularly peripheral polyneuropathy, its use as maintenance therapy was nearly abandoned. The combination of thalidomide and bortezomib has a high therapeutic potential that was accompanied by a high frequency of peripheral polyneuropathy in entry studies. After optimizing bortezomib schedule and route of administration, which lead to significant reduction in the frequency of polyneuropathy, this combination is currently a very interesting therapeutic alternative for clinical practice. This is one of the most economically available treatment regimens combining the benefits of two major drug classes in the treatment of multiple myeloma – proteasome inhibitor and imunumodulatory drugs. There is also a renewed interest in thalidomide following sharp decline in its use in recent years in the Czech Republic. Comprehensive work is focused on summarizing the long‑term experience with thalidomide, with special reference to combination with bortezomib.
Key words:
multiple myeloma – thalidomide – bortezomib – immunomodulatory drugs
Zdroje
1. Barlogie B, Tricot G, Anaissie E. Thalidomide in the management of multiple myeloma. Semin Oncol 2001; 28(6): 577– 582.
2. Singhal S, Mehta J, Desikan R et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341(21): 1565– 1571.
3. Davies FE, Raje N, Hideshima T et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001; 98(1): 210– 216.
4. Keats JJ, Chesi M, Egan JB et al. Clonal competition with alternating dominance in multiple myeloma. Blood 2012; 120(5): 1067– 1076.
5. Usmani SZ, Crowley J, Hoering A et al. Improvement in long‑term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured? Leukemia 2013; 27(1): 226– 232.
6. Cavo M, Zamagni E, Tosi P et al. Superiority of thalidomide and dexamethasone over vincristine‑ doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for mulitple myeloma. Blood 2005; (106)1: 35– 39.
7. Lokhorst HM, Breitkreuz B, van der Holt E et al. First intermin analysis of the joint HOVON‑ 50/ GMMG‑ HD3 randomized study effect of thalidomide combined with adriamycin, dexamethasone and HD melphalan in patients wit multiple myeloma. Haematologica 2005; 90 (Suppl 1): PL10.06.
8. Morgan GJ, Davies FE, Gregory WM et al. National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem‑ cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 2012; 97(3): 442– 450.
9. 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(8): 3107– 3114.
10. Facon T, Mary JY, Hulin C et al. Intergroupe Francophone du Myélome. 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(9594): 1209– 1218.
11. 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(22): 3664– 3670.
12. Wijermans P, Schaafsma M, Termorshuizen F et al. 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(19): 3160– 3166.
13. Waage A, Gimsing P, Fayers P et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010; 116(9): 1405– 1412.
14. Beksac M, Haznedar R, Firatli‑ Tuglular T et al. Addition of thalidomide to oral melphalan/ prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol 2011; 86(1): 16– 22.
15. Fayers PM, Palumbo A, Hulin C et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta‑analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 2011; 118(5): 1239– 1247.
16. Kapoor P, Rajkumar SV, Dispenzieri A et al. Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/ or transplant ineligible patients with multiple myeloma: a meta‑analysis. Leukemia 2011; 25(4): 689– 696.
17. Morgan GJ, Davies FE, Gregory WM et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood 2011; 118(5): 1231– 1238.
18. Ludwig H, Hajek R, Tóthová E et al. Thalidomide‑ dexamethasone compared with melphalan‑ prednisolone in elderly patients with multiple myeloma. Blood 2009; 11315: 3435– 3442.
19. Hájek R, Maisnar V, Krejčí M. Thalidomid. Klinická farmakologie a farmacie. 2005; 19(1): 43– 46.
20. Hájek R, Adam Z, Ščudla V et al. Doporučení vypracované Českou myelomovou skupinou, Myelomovou sekcí České hematologické společnosti a Slovenskou Myelómovou Spoločností pro diagnostiku a léčbu mnohočetného myelomu. Transfuze a hematologie dnes 2012; 18 (Suppl 1): 31– 49.
21. Durie BG. Low‑dose thalidomide in myeloma: efficacy and biologic significance. Semin Oncol 2002; 29 (6 Suppl 17): 34– 38.
22. Maisnar V, Radocha J, Büchler T et al. Monotherapy with low‑dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment. Eur J Haematol 2007; 79(4): 305– 309.
23. Ludwig H, Durie BG, McCarthy P et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood 2012; 119(13): 3003– 3015.
24. van Rhee F, Szymonifka J, Anaissie E et al. 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(8): 1220– 1227.
25. 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(24): 2946– 2955.
26. Glasmacher A, Hahn C, Hoffmann F et al. A systematic review of phase‑ II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2006; 132(5): 584– 593.
27. Prince HM, Schenkel B, Mileshkin L. An analysis of clinical trials assessing the efficacy and safety of single‑agent thalidomide in patients with relapsed or refractory multiple myeloma. Leuk Lymphoma 2007; 48(1): 46– 55.
28. Kropff M, Baylon HG, Hillengass J et al. Thalidomide versus dexamethasone for the treatment of relapsed and/ or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica 2012; 97(5): 784– 791.
29. Yakoub‑ Agha I, Mary JY, Hulin C et al. Low‑dose vs high‑dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome. Eur J Haematol 2012; 88(3): 249– 259.
30. von Lilienfeld‑ Toal M, Hahn‑ Ast C, Furkert K et al. A systematic review of phase II trials of thalidomide/ dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur J Haematol 2008; 81(4): 247– 252.
31. Zemanova M, Scudla V, Adam Z et al. Low‑dose thalidomide regimens in therapy of relapsed or refractory multiple myeloma. Neoplasma 2008; 55(4): 345– 349.
32. Krejci M, Gregora E, Straub J et al. Similar efficacy of thalidomide‑ and bortezomib‑based regimens for first relapse of multiple myeloma. Ann Hematol 2011; 90(12): 1441– 1447.
33. Minařík J, Pika T, Bačovský J et al. Thalidomid v léčbě mnohočetného myelomu po 10 letech – může nás ještě překvapit? In: Sborník abstrakt. XXVI. Olomoucké hematologické dny. Olomouc, 24.– 26. června 2012. Olomouc.
34. 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(9758): 2075– 2085.
35. 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(8): 1589– 1596.
36. Moreau P, Facon T, Attal M et al. 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. ASCO Meeting Abstracts 2010: 8014.
37. Mateos MV, Oriol A, Martinez‑ Lopez J et al. 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(10): 934– 941.
38. Palumbo A, Bringhen S, Rossi D et al. 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(34): 5101– 5109.
39. Garderet L, Iacobelli S, Moreau P et al. Superiority of the triple combination of bortezomib‑ thalidomide‑ dexamethasone over the dual combination of thalidomide‑ dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/ IFM 2005- 04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2012; 30(20): 2475– 2482.
40. Sonneveld P, Asselbergs E, Zweegman S et al. Carfilzomib combined with thalidomide and dexamethasone (CTD) is an highly effective induction and consolidation treatment in newly diagnosed patients with multiple myeloma (MM) who are transplant candidate. ASH Annual Meeting Abstracts, 2012.
41. 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(5): 431– 440.
Štítky
Paediatric clinical oncology Surgery Clinical oncologyČlánok vyšiel v časopise
Clinical Oncology
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