Continued treatment with lenalidomide in multiple myeloma

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• 作者：Jesús Martín Sánchez (1)
  
• 关键词：continued treatment ; dexamethasone ; lenalidomide ; multiple myeloma ; response
• 刊名：Advances in Therapy
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：28
• 期：8-supp
• 页码：1-13
• 全文大小：717KB
• 参考文献：1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860-873. CrossRef
  2. Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007;25:1993-999. CrossRef
  3. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-520. CrossRef
  4. Sheskin J. Thalidomide in the treatment of lepra reactions. Clin Pharm Ther. 1965;6:303-06.
  5. Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009;27:5008-014. CrossRef
  6. Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010;24:1934-939. CrossRef
  7. Lacy MQ, Allred JB, Gerz MA, et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011;118:2970-975. CrossRef
  8. Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24:22-2. CrossRef
  9. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123-132. CrossRef
  10. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133-142. CrossRef
  11. Palumbo A, Gay F, Falco P, et al. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010;28:800-07. CrossRef
  12. Kumar SK, Lacy MQ, Hayman SR, et al. Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trial. American journal of hematology. 2011;86:640-45. CrossRef
  13. Palumbo A. A phase 3 study to determine the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients = 65 years with newly diagnosed multiple myeloma (ndmm). Haematologica. 2010;95:234. Abstract 0566. CrossRef
  14. Palumbo A. A phase III trial of melphalan/prednisone/lenalidomide (MPR) versus melphalan (200 mg/m2) and autologous transplantation (MEL200) in newly diagnosed myeloma patients. J Clin Oncol (Meeting Abstracts). 2010;28:8015.
  15. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-86. CrossRef
  16. Morabito F, Gentile M, Mazzone C, et al. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2010. [Epub ahead of print]
  17. Rosinol L, Cibeira MT, Martinez J, et al. Thalidomide/dexamethasone (TD) vs. bortezomib (Velcadeamethasone (VTD) vs. VBMCP/VBAD/Velcadese III PETHEMA/Gem Trial. Blood. 2008;112. Abstract 654.
  18. 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;112:4017-023. CrossRef
  19. Ladetto M, Pagliano G, Ferrero S, et al. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010;28:2077-084. CrossRef
  20. 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;29:1627-633. CrossRef
  21. Jourdan M, Tarte K, Legouffe E, Brochier J, Rossi JF, Klein B. Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. Eur Cytokine Netw. 1999;10:65-0.
  22. Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 2001;20:4519-527. CrossRef
  23. Corral LG, Haslett PA, Muller GW, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immun. 1999;163:380-86.
  24. Muller GW, Corral LG, Shire MG, et al. Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J Med Chem. 1996;39:3238-240. CrossRef
  25. Schafer PH, Gandhi AK, Loveland MA, et al. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003;305:1222-232. CrossRef
  26. Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004;4:314-22. CrossRef
  27. Reddy N, Hernandez-Ilizaliturri FJ, Deeb G, et al. Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haem. 2008;140:36-5.
  28. Davies FE, Raje E, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98:210-16. CrossRef
  29. Chang DH, Liu N, Klimek V, et al. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood. 2006;108:618-21. CrossRef
  30. Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res. 2008:14;4650-657. CrossRef
  31. Hayashi T, Hideshima T, Akiyama M, et al. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol. 2005;128:192-03. CrossRef
  32. Tai YT, Li XF, Catley L, et al. Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications. Cancer Res. 2005;65:11712-1720. CrossRef
  33. Dredge K, Marriott JB, Todryk SM, et al. Protective antitumor immunity induced by a costimulatory thalidomide analog in conjunction with whole tumor cell vaccination is mediated by increased Th1-type immunity. J Immunol. 2002;168:4914-919.
  34. Dredge K, Marriott JB, Macdonald CD, et al. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer. 2002;87:1166-172. CrossRef
  35. Geitz H, Handt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology. 1996;31:213-21. CrossRef
  36. Payvandi F, Wu L, Haley M, et al. Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol. 2004;230:81-8. CrossRef
  37. Breitkreutz I, Raab MS. Vallet S, et al. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia. 2008;22:1925-932. CrossRef
  38. Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99:4525-530. CrossRef
  39. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin ASJ. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science. 1998;281:1680-683. CrossRef
  40. Mitsiades N, Mitsiades CS, Poulaki V, Anderson KC, Treon SP. Intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human multiple myeloma cells. Blood. 2002;99:2162-171. CrossRef
  41. Kreuz S, Siegmund D, Scheurich P, Wajant H. NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling. Mol Cell Biol. 2001;21:3964-973. CrossRef
  42. Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW. Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc Natl Acad Sci USA. 1997;94:10057-0062. CrossRef
  43. Gandhi AK, Kang J, Capone L, et al. Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets. 2010;10:155-67. CrossRef
  44. Schafer PH, Gandhi AK, Zhang LH, et al. Opposing effects of dexamethasone on lenalidomide activity in multiple myeloma: additive/synergistic effects on anti-proliferative activity on myeloma cells and antagonistic effects on immune function. ASH Annual Meeting Abstracts. 2008;112:2761.
  45. Hideshima T, Chauhan D, Shima Y, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood. 2000;96:2943-950.
  46. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Fran?ais du Myélome. N Engl J Med. 1996;335:91-7. CrossRef
  47. Harousseau JL, Avet-Loiseau H, Attal M, et al. Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 trials. J Clin Oncol. 2009;27:5720-726. CrossRef
  48. 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;26:5775-782. CrossRef
  49. Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467-473. CrossRef
  50. Martinez-Lopez J, Blade J, Mateos MV, et al. Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood. 2011;118:529-34. CrossRef
  51. Gay F, Larocca A, Wijermans P, et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2011;117:3025-031. CrossRef
  52. Niesvizky R, Richardson PG, Rajkumar SV, et al. The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma. Br J Haematol. 2008;143:46-3. CrossRef
  53. 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. CrossRef
  54. Facon T, Mary JY, 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 (IFM 99-06): a randomised trial. Lancet. 2007;370:1209-218. CrossRef
  55. Hulin C, Virion J, Leleu X, et al. Comparison of melphalan-prednisone-thalidomide (MP-T) to melphalan-prednisone (MP) in patients 75 years of age or older with untreated multiple myeloma (MM). Preliminary results of the randomized, double-blind, placebo controlled IFM 01-01 trial. J Clin Oncol (Meeting Abstracts). 2007;25:8001.
  56. 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. CrossRef
  57. Alegre A, Aguado B, Giraldo P, et al. Lenalidomide is effective as salvage therapy in refractory or relapsed multiple myeloma: analysis of the Spanish Compassionate Use Registry in advanced patients. Int J Hematol. 2011;93:351-60. CrossRef
  58. Corradini P, Cavo M, Lokhorst H, et al. Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma. Blood. 2003;102:1927-929. CrossRef
  59. Zamagni E, Nanni C, Patriarca F, et al. A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma. Haematologica. 2007;92:50-5. CrossRef
  60. Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol. 2007;25:1121-128. CrossRef
  61. Bartel TB, Haessler J, Brown TL, et al. F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood. 2009;114:2068-076. CrossRef
  62. Dimopoulos MA, Chen C, Spencer A, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23:2147-152. CrossRef
  63. 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;82:1179-184. CrossRef
  64. Niesvizky R, Javabalan 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;111:1101-109. CrossRef
  65. Attal M, Lauwers VC, Marit G, et al. Maintenance treatment with lenalidomide after transplantation for MYELOMA: final analysis of the IFM 2005-02. ASH Annual Meeting Abstracts. 2010;116:310.
  66. McCarthy PL, Owzar K, Anderson KC, et al. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma: CALGB 100104. ASH Annual Meeting Abstracts. 2010;116:37.
  67. Dimopoulos MA. Lenalidomide and dexamethasone (LEN plus DEX) treatment in relapsed/refractory multiple myeloma (RRMM) patients (pts) and risk of second primary malignancies (SPM): Analysis of MM-009/010. J Clin Oncol. 2011;29:8009. CrossRef
  68. Rossi AC, Mark TM, Jayabalan D, et al. Incidence of second primary malignancies (SPM) after 6-years follow-up of continuous lenalidomide in first-line treatment of multiple myeloma (MM). J Clin Oncol. 2011;29:8008.
  69. Palumbo AP. Incidence of second primary malignancy (SPM) in melphalan-prednisone-lenalidomide combination followed by lenalidomide maintenance (MPR-R) in newly diagnosed multiple myeloma patients (pts) age 65 or older. J Clin Oncol. 2011;29:8007. CrossRef
  70. Harousseau JL, Dimopoulos MA, Wang M, et al. The quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica. 2010;95:1738-744. CrossRef
  71. San-Miguel JF, Dimopoulos MA, Stadmauer EA, et al. Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Clin Lymphoma, Myeloma Leuk. 2011;11:38-3.
  72. Miguel JFS, Dimopoulos M, Weber D, et al. Dexamethasone dose adjustments seem to result in better efficacy and improved tolerability in patients with relapsed/refractory multiple myeloma who are treated with lenalidomide/dexamethasone (MM009/010 Sub-Analysis). ASH Annual Meeting Abstracts. 2007;110:2712.
  73. European Medicines Agency. European Medicines Agency concludes that benefit-risk balance of Revlimid remains positive. (2011). Available at http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/public_health_alerts/2011/09/human_pha_detail_000042.jsp&mid=WC0b01ac058001d126. Last accessed October 26, 2011.
  74. US Food and Drug Administration. Safety alerts for human medical products -Revlimid (lenalidomide): ongoing safety review -increased risk of developing new malignancies. (2011). Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm250606.htm. Last accessed October 26, 2011.
  75. Richardson PG, et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006;108:3458-464. CrossRef
  76. Richardson P, Blood E, Mitsiades CS, et al. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood. 2009;114:772-78. CrossRef
  77. Palumbo A, Gay F. How to treat elderly patients with multiple myeloma: combination of therapy or sequencing. Hematology. 2009:566-77.
  78. San-Miguel JF, Mateos MV. How to treat a newly diagnosed young patient with multiple myeloma. Hematology. 2009;555-65.
  
• 作者单位：Jesús Martín Sánchez (1)
  
  1. Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla, Avenida Manuel Siurot s/n, 41013, Sevilla, Spain
  

文摘

Lenalidomide is a more potent and better tolerated immunomodulatory drug (IMiD) as compared to thalidomide, the first-in-class IMiD. The mechanism of action of lenalidomide in multiple myeloma (MM) includes direct antitumor, immunomodulatory, and regulatory effects on the plasma cell-bone marrow niche interaction. Lenalidomide in combination with dexamethasone has shown a significantly higher efficacy as compared to dexamethasone alone in the treatment of relapsed or refractory MM in terms of overall response (OR) rate, complete response (CR) rate, time to progression (TTP), and overall survival (OS). Dosing, duration, and overall benefit of dexamethasone combination remains to be elucidated in ad-hoc trials, which may impact the tolerability and efficacy of the recommended schedule of lenalidomide rescue treatment. Depth of response achieved with lenalidomide and dexamethasone is associated with improvements in response duration, TTP, and OS, regardless of when the response is achieved. Although the probability of achieving a CR or very good partial response (VGPR) decreases over time, patients who are able to tolerate treatment in the absence of disease progression continue to experience benefits. However, optimal duration of rescue treatment from the time-point of best response has not been formally established. Recent data from phase 3 clinical trials also suggest the benefit of single-agent lenalidomide as maintenance after first-line treatment, and of lenalidomide combination therapy with conventional chemotherapy or new agents as induction treatment, in both autologous stem cell transplantation (ASCT) eligible and ineligible MM patients. Concerns about second primary neoplasms have been recently raised, and need further investigation. Taken together, these facts open new clinical settings in which lenalidomide therapy may benefit MM patients and deepen IMiD knowledge, especially in the continued rescue treatment and maintenance settings. Further study is warranted to optimize treatment with IMiDs.