The clinical safety of lenalidomide in multiple myeloma and myelodysplastic syndromes

Expert Opinion on Drug Safety

Volumn 11, Issue 1, 2012, Pages 107-120

  Palumbo, Antonio ^a   Freeman, John ^b   Weiss, Lilia ^b   Fenaux, Pierre ^c  

^a UNIVERSITY OF TURIN   (Italy)

^b CELGENE CORPORATION   (United States)

^c AVICENNE HOSPITAL   (France)

Author keywords

Adverse events; Lenalidomide; Multiple myeloma; Myelodysplastic syndromes; Myelosuppression; Thromboembolism

Indexed keywords

ACETYLSALICYLIC ACID; ALKYLATING AGENT; ANTIHISTAMINIC AGENT; BORTEZOMIB; DEXAMETHASONE; IMID; LENALIDOMIDE; LOW MOLECULAR WEIGHT HEPARIN; MELPHALAN; PLACEBO; PREDNISONE; REVASSIST; STEROID; THALIDOMIDE; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ARTICLE; ASTHENIA; BACTERIAL INFECTION; BLEEDING DISORDER; BLOOD CELL COUNT; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER INCIDENCE; CANCER MORTALITY; CANCER PATIENT; CANCER RISK; CEREBROVASCULAR ACCIDENT; CHROMOSOME 5Q; CHROMOSOME DELETION 5; CLINICAL TRIAL (TOPIC); CONSTIPATION; CREATININE CLEARANCE; DEEP VEIN THROMBOSIS; DIARRHEA; DISEASE COURSE; DRUG DOSE REDUCTION; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; FATIGUE; HEART INFARCTION; HUMAN; HYPERGLYCEMIA; HYPOKALEMIA; HYPOTHYROIDISM; KIDNEY DYSFUNCTION; KIDNEY FAILURE; LOW DRUG DOSE; LUNG EMBOLISM; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MUSCLE CRAMP; MYCOSIS; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUROTOXICITY; NEUTROPENIA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; POSTMARKETING SURVEILLANCE; PRIMARY TUMOR; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECURRENT DISEASE; SECOND CANCER; SKIN MANIFESTATION; STEM CELL TRANSPLANTATION; TERATOGENICITY; THROMBOCYTOPENIA; VENOUS THROMBOEMBOLISM; VIRUS INFECTION;

ADMINISTRATION, ORAL; ANTINEOPLASTIC AGENTS; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROMES; PRODUCT SURVEILLANCE, POSTMARKETING; RENAL INSUFFICIENCY; THALIDOMIDE; TIME FACTORS;

EID: 84555217850     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2011.619975     Document Type: Article

References (102)

1. REVLIMID (lenalidomide) Prescribing Information (PI). Celgene Corp., Summit, NJ 07901, USA. January 2009. Available from: http://www.revlimid. com/pdf/REVLIMID-PI.pdf
2. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007;357:2133-42 (Pubitemid 350146108)
3. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007;357:2123-32 (Pubitemid 350146107)
4. 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;28:800-7
5. Harousseau JL, Dimopoulos MA, Wang M, et al. Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica 2010;95:1738-44
6. San Miguel JF, Dimopoulos MA, Stadtmauer 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;11:38-43
7. Dimopoulos MA, Palumbo A, Attal M, et al. Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia 2011;25:749-60
8. 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;96:2943-50
9. Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99:4525-30 (Pubitemid 34627223)
10. Verhelle D, Corral LG, Wong K, et al. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res 2007;67:746-55 (Pubitemid 46192215)
11. Escoubet-Lozach L, Lin I-L, Jensen-Pergakes K, et al. Pomalidomide and lenalidomide induce p21WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res 2009;69:7347-56
12. 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
13. 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 (Pubitemid 44061362)
14. Noonan KA, Ferguson A, Huff CA, et al. The immunomodulatory role of lenalidomide on Prevnar responses in patients with relapsed multiple meyloma: a comprehensive analysis of the immune response. Blood 2008;112:abstract 2772
15. 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;14:4650-7
16. Baz R, Dimopoulos M, Richardson P, et al. Lenalidomide-based therapy leads to improvement of humoral immune system in relapsed or refractory multiple myeloma patients who respond to the therapy. Haematologica 2009;94:abstract 0395
17. Lioznov M, El-Cheikh J Jr, Hoffmann F, et al. Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells. Bone Marrow Transplant 2010;45:349-53
18. Lopez-Girona A, Mendy D, Brady H, et al. Lenalidomide inhibits the multiple myeloma cell survival factor IRF4/MUM1. Clin Lymphoma Myeloma 2009;9(Suppl 1):abstract 309
19. Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivative augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98:210-16
20. Marriott JB, Clarke IA, Dredge K, et al. Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4(+) and CD8(+) T cells. Clin Exp Immunol 2002;130:75-84
21. Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev 2010;24:S13-19
22. 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 Immunol 1999;163:380-6 (Pubitemid 29295864)
23. Dredge K, Horsfall R, Robinson SP, et al. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res 2005;69:56-63 (Pubitemid 40410468)
24. Giagoundis AA, Germing U, Aul C. Biological and prognostic significance of chromosome 5q deletions in myeloid malignancies. Clin Cancer Res 2006;12:5-10 (Pubitemid 43166169)
25. Graubert TA, Payton MA, Shao J, et al. Integrated genomic analysis implicates haploinsufficiency of multiple chromosome 5q31.2 genes in de novo myelodysplastic syndromes pathogenesis. PLoS ONE 2009;4:e4583
26. Eisenmann KM, Dykema KJ, Matheson SF, et al. 5q-myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics. Oncogene 2009;28:3429-41
27. Pellagatti A, Jadersten M, Forsblom AM, et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q-syndrome patients. Proc Natl Acad Sci USA 2007;104:11406-11 (Pubitemid 47175153)
28. Wei S, Chen X, Rocha K, et al. A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci USA 2009;106:12974-9
29. Tehranchi R, Woll PS, Anderson K, et al. Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med 2010;363:1025-37
30. Ramsay AG, Johnson AJ, Lee AM, et al. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Investig 2008;118:2427-37 (Pubitemid 351949771)
31. Ramsay AG, Clear AJ, Kelly G, et al. Follicular lymphoma cells induce T-cell immunological synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy. Blood 2009;114:4713-20
32. Gaidarova S, Mendy D, Heise C, et al. Lenalidomide induced capping of CD20 and cytoskeleton proteins to enhance rituximab immune recognition of malignant B-cells. Blood 2010;116:abstract 2845
33. Ximeri M, Galanopoulos A, Klaus M, et al. Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndromes associated with chromosome 5q deletion. Haematologica 2010;95:406-14
34. Ebert BL, Galili N, Tamayo P, et al. An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome. PLoS Med 2008;5:e35
35. Buesche G, Dieck S, Giagounidis A, et al. Anti-angiogenic in-vivo effect of lenalidomide and its impact on neoplastic and non-neoplastic hematopoiesis in MDS with del(5q) chromosome abnormality. Blood 2009;114:abstract 3800
36. Chen N, Lau H, Kong L, et al. Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol 2007;47:1466-75 (Pubitemid 350115306)
37. 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;23:2147-52
38. 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;11:29-37
39. McCarthy P, Owzar K, Anderson K, et al. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB ECOG BMT-CTN 100104. Haematologica 2011;96(S1):S23
40. Attal M, Olivier P, Cances V, et al. Maintenance treatment with lenalidomide after transplantation for myeloma: analysis of secondary malignancies within the IFM2005-02 trial. Haematologica 2011;96(S1):S23
41. Palumbo A, Delforge M, Catalano J, et al. A phase 3 study evaluating the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients ‡ 65 years with newly diagnosed multiple myeloma (NDMM): continuous use of lenalidomide vs fixed-duration regimens. Blood 2010;116:abstract 622
42. List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549-57 (Pubitemid 40204668)
43. List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355:1456-65 (Pubitemid 44511560)
44. Fenaux P, Giagounidis A, Selleslag D, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood 2011;118:3765-76
45. List AF, Giagounidis A, Backstrom JT, et al. Early lenalidomide (LEN) dose intensity and durable RBC-transfusion independence (RBC-TI) in patients (pts) with low-/int-1-risk myelodysplastic syndromes (MDS) and del5q. J Clin Oncol 2011;abstract 6522; ASCO abstract accepted for publication
46. Kurtin SE, List AF. Durable long-term responses in patients with myelodysplastic syndromes treated with lenalidomide. Clin Lymphoma Myeloma 2009;9:E10-13
47. Ades L, Boehrer S, Prebet T, et al. Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study. Blood 2009;113:3947-52
48. Raza A, Reeves JA, Feldman EJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 2008;111:86-93
49. 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;9:145-50
50. Fenaux P, Giagounidis A, Selleslag DL, et al. Safety of lenalidomide (LEN) from a randomized phase 3 trial (MDS-004) in low-/int-1-risk myelodysplastic syndromes (MDS) with a del(5q) abnormality. J Clin Oncol 2010;28(Suppl 15S):abstract 6598
51. Ishak J, Dimopoulos MA, Weber D, et al. Declining rates of adverse events and dose modifications with lenalidomide in combination with dexamethasone. Blood 2008;111:abstract 3708
52. Lonial S, Baz R, Swern AS, et al. Neutropenia is a predictable and early event in affected patients with relapsed/refractory multiple myeloma treated with lenalidomide in combination with dexamethasone. Blood 2009;114:abstract 2879
53. Palumbo A, Dimopoulos MA, Delforge M, et al. A Phase 3 study to determine the efficacy and safety of lenalidomide combined with melphalan and prednisone (MPR) in patients ‡ 65 years with newly diagnosed multiple myeloma (NDMM). EHA 2010;abstract 0566
54. Attal M, Cristini C, Marit G, et al. Maintenance treatment with lenalidomide after transplantation for myeloma: final analysis of the IFM 2005-02. Blood 2010;116:310
55. McCarthy PL, Owzar K, Anderson KC, et al. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplant (AHSCT) for multiple myeloma: CALGB 100104. Blood 2010;116:37
56. Sekeres MA, Maciejewski JP, Giagounidis AA, et al. Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 2008;26:5943-9
57. Giagounidis A, Fenaux P, Mufti GJ, et al. Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes. Ann Hematol 2008;87:345-52
58. Srkalovic G, Cameron MG, Rybicki L, et al. Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer 2004;101:558-66 (Pubitemid 38970607)
59. Richardson P, Jagannath S, Hussein M, et al. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009;114:772-8
60. Zonder JA, Crowley J, Hussein MA, et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (SO232). Blood 2010;116:5838-41
61. Knight R, DeLap RJ, Zeldis JB. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 2006;354:2079-80
62. Niesvizky R, Spencer A, Wang M, et al. Increased risk of thrombosis with lenalidomide in combination with dexamethasone and erythropoietin. J Clin Oncol 2006;24(Suppl 18S):abstract 7506
63. Zangari MZ, Tricot G, Polavaram L, et al. Survival effect of venous thromboembolism in patients with multiple myeloma treated with leanlidomide and high-dose dexamethasone. J Clin Oncol 2010;28:132-5
64. Klein U, Kosely F, HillengaB J, et al. Effective prophylaxis of thromboembolic complications with low molecular weight heparin in relapsed multiple myeloma patients treated with lenalidomide and dexamethasone. Ann Hematol 2009;88:67-71
65. 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)
66. Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050-3 (Pubitemid 41775908)
67. Larocca A, Caravita Di Toritto T, Di Raimondo F, et al. Thromboprophylaxis for newly-diagnosed multiple myeloma patients treated with lenalidomide-based regimens: an interim analysis of a prospective, randomized study of enoxaparin vs aspirin. Haematologica 2010;95(S3):abstract C029
68. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide-and lenalidomide-associated thrombosis in myeloma. Leukemia 2008;22:414-23 (Pubitemid 351255436)
69. Delforge M, Facon T, Bravo M-L, et al. Lenalidomide plus dexamethasone has similar tolerability and efficacy in treatment of relapsed/refractory multiple myeloma patients with or without history of neuropathy. Blood 2009;114:abstract 3873
70. Bwire R, Freeman J, Houn F. Managing the teratogenic risk of thalidomide and lenalidomide: an industry perspective. Expert Opin Drug Saf 2011;10:3-8
71. Forrest DL, Nevill TJ, Naiman SC, et al. Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis. Bone Marrow Transplant 2003;32:915-23 (Pubitemid 37369270)
72. Youlden DR, Baade PD. The relative risk of second primary cancers in Queensland, Australia: a retrospective cohort study. BMC Cancer 2011;11:83
73. Dores GM, Cote TR, Travis LB. Chapter 16 from: New malignancies among cancer survivors: SEER Cancer Registries, 1973-2000. Published 2006
74. Dong C, Hemminki K. Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958-1996: a search for common mechanisms. Br J Cancer 2001;85:997-1005 (Pubitemid 33016003)
75. Morton L, Curtis RE, Linet MS, et al. Second malignancy risks after non-Hodgkin's lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol 2010;28:4935-44
76. Palumbo A, Bringhen S, Zweegman S, et al. Secondary malignancies in elderly myeloma patients. Haematologica 2011;96(S1):S24
77. Palumbo A, Delforge M, Catalano J, et al. 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; abstract 8007; ASCO abstract accepted for publication
78. Howlander N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2008, National Cancer Institute, Bethesda, MD, based on November 2010 SEER data submission, posted to SEER web site, 2011. Available from: http://seer.cancer.gov/csr/1975-2008/
79. Dimopoulos M, Orlowski R, Niesvizky R, et al. Lenalidomide and dexamethasone (Len + 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;abstract 8009; ASCO abstract accepted for publication
80. Morgan G, Durie B, San Miguel J, et al. Retrospective analysis of the long term safety of lenalidomide (Len) ± dexamethasone (Dex) in relapsed/refractory multiple myeloma (RRMM) patients (pts): analysis of pooled data and incidence rates (IR) of second primary malignancy (SPM). Haematologica 2011;96(S1):S24
81. Germing U, Lauseker M, Hildebrandt B, et al. Survival, prognostic factors, and rates of leukemic transformation in a multicenter study of 303 untreated patients with MDS and del(5q). Blood 2009;114:abstract 945
82. Battiwalla M, Fu T, Knight RD, List AF. Impact of age on transfusion independence response, survival, and transformation to acute myeloid leukaemia in patients with deletion 5q: A sub-analysis of the MDS-003 study. Blood 2008;112:abstract 5071
83. Battiwalla M, Fu T, Knight RD, List AF. Impact of baseline renal function on transfusion-independence response, survival, and transformation to acute myeloid leukaemia in patients with Deletion 5q: A sub-analysis of the MDS-003 study. Blood 2008;112:abstract 5088
84. Ades L, Lebras F, Sebert M, et al. Risk of AML evolution in lower risk MDS with del 5q treated with or without lenalidomide. A report by the Groupe Francophone des Myelodysplasies (GFM). Blood 2010;116:abstract 976
85. Gohring G, Giagounidis A, Busche G, et al. Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression. Ann Hematol 2010;89:365-74
86. Dimopoulos MA, Alegre A, Stadtmauer EA, et al. The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function. Cancer 2010;116:3807-14
87. Dimopoulos MA, Dimitrios C, Roussou M, et al. Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment. Eur J Haematol 2010;85:1-5
88. Ludwig H, Spicka I, Thaler J, et al. Lenalidomide-dexamethasone (LD) for reversal of acute light chain-induced renal failure (ARF) in multiple myeloma (MM). results from a phase II study. Haematologica 2011;96(S1):abstract P-225
89. de la Rubia J, Roig M, Ibáñez A, et al. Activity and safety of lenalidomide and dexamethasone in multiple myeloma patients requiring dialysis: a Spanish multicentre retrospective study. EurJ Haematol 2010;85:363-5
90. Palumbo A, Facon T, Sonneveld P, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood 2008;111:3968-77
91. 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)
92. Baz R, Walker E, Karam MA, et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol 2006;17:1766-71 (Pubitemid 44884050)
93. Lehmann F, Jean E-C, Zabelina T, et al. Lenalidomide after allogeneic stem cell transplantation in multiple myeloma. Blood 2007;110:abstract 4840
94. Kelaidi C, Park S, Brechignac S, et al. Treatment of myelodysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide. Leuk Res 2008;32:1049-53
95. Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36
96. Heise C, Carter T, Schafer P, Chopra R. Pleiotropic mechanisms of action of lenalidomide efficacy in del(5q) myelodysplastic syndromes. Expert Rev Anticancer Ther 2010;10:1663-7
97. Sekeres MA, Gundacker H, Lancet J, et al. A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: SWOG Study S0605. Blood 2011; 118:523-8
98. Platzbecker U, Haase D, Braulke F, et al. A phase I study of a combination of 5-azacitidine followed by lenalidomide in high-risk MDS or AML patients with chromosome 5 abnormalities-interim results of the "AZALE" trial. Blood 2010;116:abstract 4000
99. Sekeres MA, List AF, Cuthbertson D, et al. Phase I combination trial of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes. J Clin Oncol 2010;28:2253-8
100. Sekeres MA, O'Keefe C, List AF, et al. Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher-risk myelodysplastic syndromes. Am J Hematol 2011;86:102-3
101. Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q-syndrome gene by RNA interference screen. Nature 2008;451(7176):335-9
102. Oliva EN, Cuzzola M, Nobile F, et al. Changes in RPS14 expression levels during lenalidomide treatment in Low-and Intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion. Eur J Haematol 2010;85:231-5