Update on immunomodulatory drugs (IMiDs) in hematologic and solid malignancies

Expert Opinion on Pharmacotherapy

Volumn 13, Issue 4, 2012, Pages 473-494

  Vallet, Sonia ^a   Witzens Harig, Mathias ^a   Jaeger, Dirk ^a   Podar, Klaus ^a,b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Angiogenesis; Birth defects; Cereblon; Immunomodulation; Lenalidomide; Multiple myeloma; Myelodysplastic syndromes; Pomalidomide; Thalidomide

Indexed keywords

APREMILAST; BENDAMUSTINE; BEVACIZUMAB; BORTEZOMIB; CARFILZOMIB; CC 10015; CC 11006; CLARITHROMYCIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; IMMUNOGLOBULIN LIGHT CHAIN; IMMUNOMODULATING AGENT; LENALIDOMIDE; MELPHALAN; NPI 005; PERIFOSINE; POMALIDOMIDE; PREDNISONE; RITUXIMAB; TEMSIROLIMUS; THALIDOMIDE; THALIDOMIDE DERIVATIVE; UNCLASSIFIED DRUG;

ACUTE LEUKEMIA; AMYLOIDOSIS; ANTIANGIOGENIC ACTIVITY; APOPTOSIS; CANCER RELAPSE; CHRONIC LYMPHATIC LEUKEMIA; CLASSICAL HODGKIN LYMPHOMA; COLON CARCINOMA; CONSTIPATION; DEEP VEIN THROMBOSIS; DIARRHEA; DROWSINESS; DRUG DOSE ESCALATION; DRUG MEGADOSE; DRUG TOLERABILITY; ENDOMETRIUM CANCER; ERYTHROBLAST; ERYTHROPOIESIS; FATIGUE; HEMATOLOGIC MALIGNANCY; HEMOGLOBIN SYNTHESIS; HUMAN; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LOW DRUG DOSE; LUNG EMBOLISM; LUNG NON SMALL CELL CANCER; LYMPHOMA; MELANOMA; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELOFIBROSIS; MYELOID METAPLASIA; NEUROPATHY; NEUTROPENIA; NONHODGKIN LYMPHOMA; PARESTHESIA; POEMS SYNDROME; PROSTATE CANCER; REVIEW; SOLID TUMOR; T CELL LYMPHOMA; TERATOGENICITY; THROMBOCYTOPENIA; THROMBOSIS; THYROID CANCER; UNSPECIFIED SIDE EFFECT; VENOUS THROMBOEMBOLISM; WALDENSTROEM MACROGLOBULINEMIA;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOLOGIC FACTORS; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROMES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; THALIDOMIDE;

EID: 84857308611     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2012.656091     Document Type: Review

References (188)

1. 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)
2. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011;364:1046-60
3. Scheindlin S. The courage of one's convictions: the due diligence of Frances Oldham Kelsey at the FDA. Mol Interv 2011;11:3-9
4. McBride WG. Teratogenic action of thalidomide. Lancet 1978;1:1362 (Pubitemid 8367144)
5. Brent RL. The contributions of Widukind Lenz to teratology and science: comments on "Thalidomide retrospective: what did the clinical teratologist learn?" Teratology. 1992;46:415-16
6. Sheskin J. Further observation with thalidomide in lepra reactions. Lepr Rev 1965;36:183-7
7. Iyer CG, Languillon J, Ramanujam K, et al. WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients. Bull World Health Organ 1971;45:719-32
8. Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 2004;4:314-22 (Pubitemid 38525287)
9. Sampaio EP, Sarno EN, Galilly R, et al. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991;173:699-703
10. D'Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994;91:4082-5 (Pubitemid 24139577)
11. Vacca A, Ribatti D, Roncali L, et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994;87:503-8 (Pubitemid 24230014)
12. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341:1565-71
13. Zeldis JB, Williams BA, Thomas SD, et al. S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide. Clin Ther 1999;21:319-30 (Pubitemid 29157790)
14. Hayashi T, Hideshima T, Akiyama M, et al. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol 2005;128:192-203
15. Fujita K, Asami Y, Tanaka K, et al. Antiangiogenic effects of thalidomide: expression of apoptosis-inducible active-caspase-3 in a three-dimensional collagen gel culture of aorta. Histochem Cell Biol 2004;122:27-33 (Pubitemid 39070590)
16. Yabu T, Tomimoto H, Taguchi Y, et al. Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate. Blood 2005;106:125-34 (Pubitemid 40967183)
17. 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
18. Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science 2011;327:1345-50
19. Meiler SE, Wade M, Kutlar F, et al. Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. Blood 2011;118:1109-12
20. Gordon JN, Prothero JD, Thornton CA, et al. CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-alpha and MMP-3 production in patients with inflammatory bowel disease. J Crohn's Colitis 2009;3:175-82
21. Baughman RP, Judson MA, Ingledue R, et al. Efficacy and safety of apremilast in chronic cutaneous sarcoidosis. Arch Dermatol 17 Oct 2011 [Epub ahead of print]
22. McCann FE, Palfreeman AC, Andrews M, et al. Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. Arthritis Res Ther 2010;12:R107
23. Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 2010;159:842-55
24. 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)
25. 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)
26. Larocca A, Cavallo F, Bringhen S, et al. Aspirin or enoxaparin thromboprophylaxis for newly-diagnosed multiple myeloma patients treated with lenalidomide. Blood 2012;119(4):933-9
27. Thornburg A, Abonour R, Smith P, et al. Hypersensitivity pneumonitis-like syndrome associated with the use of lenalidomide. Chest 2007;131:1572-4 (Pubitemid 46762369)
28. Chanan-Khan A, Miller KC, Lawrence D, et al. Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response. Cancer 2011;117:2127-35
29. Attal M, Lauwers VC, Marit G, et al. Maintenance treatment with lenalidomide after transplantation for myeloma: final analysis of the IFM 2005-02. Blood 2010;116:310
30. Palumbo A, Delforge M, Catalano J, et al. A phase III 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;116:622
31. 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. Blood 2010;116:37
32. Mailankody S, Pfeiffer RM, Kristinsson SY, et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 2011;118:4086-92
33. Palumbo A, Larocca A, Zweegman S, et al. Second primary malignancies in newly diagnosed multiple myeloma patients treated with lenalidomide: analysis of pooled data in 2459 patients. Blood 2011;118:455; abstract 996
34. Ades L, Lebras F, Sebert M, et al. Treatment with Lenalidomide does not appear to increase the risk of leukemia progression in lower risk myelodysplastic syndrome with 5q deletion. A comparative analysis by the GFM. Haematologica. Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 21993675# 2012 Feb;97(2):213-8
35. Christian MS, Laskin OL, Sharper V, et al. Evaluation of the developmental toxicity of lenalidomide in rabbits. Birth Defects Res B Dev Reprod Toxicol 2007;80:188-207 (Pubitemid 47047368)
36. LeBlanc R, Hideshima T, Catley LP, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood 2004;103:1787-90 (Pubitemid 38268973)
37. 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;305:1222-32 (Pubitemid 36618002)
38. Gorgun G, Calabrese E, Soydan E, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood 2011;116:3227-37
39. Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98:210-16
40. Benson DM Jr, Bakan CE, Zhang S, et al. IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood 2011;118:6387-91
41. Available from: http://clinicaltrials.gov
42. Dredge K, Marriott JB, Macdonald CD, et al. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer 2002;87:1166-72 (Pubitemid 35418112)
43. 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)
44. Lentzsch S, Rogers MS, LeBlanc R, et al. S-3-Aminophthalimido- glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice. Cancer Res 2002;62:2300-5 (Pubitemid 34411708)
45. Gupta D, Treon SP, Shima Y, et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia 2001;15:1950-61 (Pubitemid 33115003)
46. De Luisi A, Ferrucci A, Coluccia AM, et al. Lenalidomide restrains motility and overangiogenic potential of bone marrow endothelial cells in patients with active multiple myeloma. Clin Cancer Res 2011;17:1935-46
47. Xu Y, Li J, Ferguson GD, et al. Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases. Blood 2009;114:338-45
48. 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)
49. 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
50. 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)
51. Heise C, Carter T, Schafer P, et al. Pleiotropic mechanisms of action of lenalidomide efficacy in del(5q) myelodysplastic syndromes. Expert Rev Anticancer Ther 2010;10:1663-72
52. Lopez-Girona A, Heintel D, Zhang LH, et al. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol 2011;154:325-36
53. Li S, Pal R, Monaghan SA, et al. IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM. Blood 2011;117:5157-65
54. Anderson KC. Lenalidomide and thalidomide: mechanisms of action - similarities and differences. Semin Hematol 2005;42:S3-8 (Pubitemid 41774591)
55. Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the anti-myeloma activity of lenalidomide and pomalidomide. Blood 2011;118:4771-9
56. Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, et al. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res 2009;69:7347-56
57. Jakubikova J, Adamia S, Kost-Alimova M, et al. Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications. Blood 2011;117:4409-19
58. 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)
59. Gandhi AK, Kang J, Verhelle D, et al. Inhibition of cell proliferation by lenalidomide is associated with stimulation of Egr1 transcriptional activity in a chromosome 5 deleted Burkitt's lymphoma and multiple myeloma cell line. J Clin Oncol 2007;25:8110
60. Moutouh-de Parseval LA, Verhelle D, Glezer E, et al. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest 2008;118:248-58
61. Basiorka AA, McGraw K, Clark MS, et al. Lenalidomide upregulates erythropoietin receptor expression in hematopoietic progenitors by modulating receptor rurnover. Blood 2011;118:1026; abstract 2382
62. Liu A, Donnenberg V, Li S, et al. Immunomodulatory drugs lenalidomide and pomalidomide inhibit the maturation of megakaryocytes by suppressing the expression of GATA1. Blood 2011;118:801; abstract 1840
63. Munemasa S, Sakai A, Kuroda Y, et al. Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation. Int J Oncol 2008;33:129-36
64. Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia 2008;22:1925-32
65. Pal R, Monaghan SA, Hassett AC, et al. Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia. Blood 2010;115:605-14
66. Kumar SK, Dingli D, Dispenzieri A, et al. Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT. Bone Marrow Transplant 2008;41:1013-19 (Pubitemid 352034176)
67. 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 III study. Lancet 2010;376:2075-85
68. Rosinol L, Cibeira MT, Mateos MV, et al. A phase III PETHEMA/GEM study of induction therapy prior autologous stem cell transplantation (ASCT) In multiple myeloma: superiority of VTD (bortezomib/ thalidomide/dexamethasone) over TD and VBMCP/VBAD plus bortezomib. Blood 2010;116:307
69. Moreau P, Avet-Loiseau H, Facon T, et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment prior to autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood 2011;118:5752-8
70. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009;27:1788-93
71. 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;28:2077-84
72. 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)
73. 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
74. 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;28:3160-6
75. Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010;116:1405-12
76. Kumar A, Hozo I, Wheatley K, et al. Thalidomide versus bortezomib based regimens as first-line therapy for patients with multiple myeloma: a systematic review. Am J Hematol 2011;86:18-24
77. Ludwig H, Hajek R, Tothova E, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009;113:3435-42
78. Palumbo A, Attal M, Roussel M. Shifts in the therapeutic paradigm for patients newly diagnosed with multiple myeloma: maintenance therapy and overall survival. Clin Cancer Res 2011;17:1253-63
79. Roussel M, Facon T, Moreau P, et al. Firstline treatment and maintenance in newly diagnosed multiple myeloma patients. Recent Results Cancer Res 2011;183:189-206
80. Sonneveld P, Schmidt-Wolf I, van der Holt B, et al. HOVON-65/ GMMG-HD4 randomized phase III trial comparing bortezomib, doxorubicin, dexamethasone (PAD) vs VAD followed by high-dose melphalan (HDM) and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma (MM). Blood 2010;116:23; abstract 40
81. Stewart AK, Trudel S, Bahlis NJ, et al. A randomized phase III trial of thalidomide and prednisone as maintenance therapy following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM): the NCIC CTG MY.10 Trial. Blood 2010;116:39
82. Richardson PG, Schlossman RL, Weller E, et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002;100:3063-7 (Pubitemid 35217050)
83. Lonial S, Jakubowiak AJ, Jagannath S, et al. A phase II study of elotuzumab in combination with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma. Blood 2011;118:141; abstract 303
84. Wang M, Bensinger W, Martin T, et al. Interim results from PX-171-006, a phase II multicenter dose-expansion study of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed and/ or refractory multiple myeloma. J Clin Oncol 2011;29:abstract 8025
85. Moreau P, Palumbo A, Stewart AK, et al. A randomized, multicenter, phase (Ph) III study comparing carfilzomib (CFZ), lenalidomide (LEN), and dexamethasone (Dex) to LEN and Dex in patients (Pts) with relapsed multiple myeloma (MM). J Clin Oncol 2011;29:abstract TPS225
86. Lentzsch S, O'Sullivan A, Kennedy R, et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with refractory or relapsed multiple myeloma is safe and highly effective: results of phase I/II open-label, dose escalation study. Blood 2011;118:142
87. 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
88. Roussel M, Robillard N, Moreau P, et al. Bortezomib, lenalidomide, and dexamethasone (VRD) consolidation and lenalidomide maintenance in frontline multiple myeloma patients: updated results of the IFM 2008 phase II VRD intensive program. Blood 2011;118: 816; abstract 1872
89. Jakubowiak AJ, Dytfeld D, Jagannath S, et al. Final results of a frontline phase I/ II study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in multiple myeloma (MM). Blood 2011;118:288; abstract 631
90. Mark T, Stern J, Furst JR, et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant 2008;14:795-8 (Pubitemid 351773154)
91. Kumar S, Giralt S, Stadtmauer EA, et al. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens. Blood 2009;114:1729-35
92. DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720-6
93. Giralt S, Stadtmauer EA, Harousseau JL, et al. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia 2009;23:1904-12
94. Duarte RF, Shaw BE, Marin P, et al. Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. Bone Marrow Transplant 2011;46:52-8
95. Micallef IN, Ho AD, Klein LM, et al. Plerixafor (Mozobil) for stem cell mobilization in patients with multiple myeloma previously treated with lenalidomide. Bone Marrow Transplant 2011;46:350-5
96. Sinha S, Gertz MA, Lacy MQ, et al. Majority of patients receiving initial therapy with lenalidomide-based regimens can be successfully mobilized with appropriate mobilization strategies. Leukemia 28 Oct 2011 [Epub ahead of print]
97. Brave M, Farrell A, Ching Lin S, et al. FDA review summary: mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Oncology 2010;78:282-8
98. 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
99. 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)
100. Hofmeister CC, Yang X, Pichiorri F, et al. Phase I trial of lenalidomide and CCI-779 in patients with relapsed multiple myeloma: evidence for lenalidomide-CCI-779 interaction via P-glycoprotein. J Clin Oncol 2011;29:3427-34
101. Harada T, Ozaki S, Oda A, et al. Combination therapy of a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide significantly enhances myeloma cell cytotoxicity via antibody-dependent cellular cytotoxicity. Blood 2011;118:799; abstract 1833
102. Santo L, Vallet S, Hideshima T, et al. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene 2011;29:2325-36
103. Chauhan D, Singh AV, Ciccarelli B, et al. Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma. Blood 2011;115:834-45
104. Lacy MQ, Allred JB, Gertz 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;118:2970-5
105. Schey SA, Fields P, Bartlett JB, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004;22:3269-76 (Pubitemid 41103682)
106. Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 2009;27:5008-14
107. 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;24:1934-9
108. Palumbo A, Larocca A, Carella AM, et al. A phase I/II study of pomalidomide-cyclophosphamideprednisone (PCP) in patients with multiple myeloma relapsed/refractory to lenalidomide. Blood 2011;118: 289; abstract 632
109. Richardson PG, Siegel D, Baz R, et al. A phase I/II multi-center, randomized, open label dose escalation study to determine the maximum tolerated dose, safety, and efficacy of pomalidomide alone or In combination with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide and bortezomib. Blood 2010;116:864
110. Richardson PG, Siegel DS, Vij R, et al. Randomized, open label phase I/II study of pomalidomide (POM) alone or in combination with low-dose dexamethasone (LoDex) in patients (Pts) with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide (LEN) and bortezomib (BORT): phase II results. Blood 2011118:290; abstract 634
111. Leleu X, Attal M, Arnulf B, et al. High response rates to pomalidomide and dexamethasone in patients with refractory myeloma, final analysis of IFM 2009-02. Blood 2011;118: 369; abstract 812
112. Mark TM, Rodriguez M, Shah M, et al. ClaPD (clarithromycin/[Biaxin-], pomalidomide, dexamethasone) therapy in relapsed or refractory multiple myeloma. 2011;118:291; abstract 635
113. Short KD, Rajkumar SV, Larson D, et al. Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma. Leukemia 2011;25:906-8
114. Raza A, Reeves JA, Feldman EJ, et al. Phase II 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
115. Fowler NH, McLaughlin P, Hagemeister FB, et al. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 2010;28(Suppl):abstract 8036
116. Fenaux P, Giagounidis A, Selleslag D, et al. A randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood 2011;118:3765-76
117. El-Sherbiny YM, Meade JL, Holmes TD, et al. The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Res 2007;67:8444-9 (Pubitemid 47437416)
118. Fowler N, McLaughlin P, Hagemeister FB, et al. A biologic combination of lenalidomide and rituximab for front-line therapy of indolent B-cell non-Hodgkin's lymphoma. Blood 2009;114: 1714
119. Dutia M, DeRoock I, Chee K, et al. R2: preliminary results of a phase II study of lenalidomide and rituximab in relapsed/ refractory indolent non-Hodgkin's lymphoma (NHL). Blood 2009;114
120. Dutia M, DeRoock I, Chee K, et al. Analysis of phase II study of lenalidomide and rituximab in relapsed or refractory non-Hodgkin's lymphoma. Haematologica 2010;abstract 0295
121. Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 2008;26:4952-7
122. Habermann TM, Lossos IS, Justice G, et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 2009;145:344-9
123. Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non- Hodgkin's lymphoma. Ann Oncol 2011;22:1622-7
124. Czuczman MS, Vose JM, Witzig TE, et al. The differential effect of lenalidomide monotherapy in patients with relapsed or refractory transformed non-Hodgkin lymphoma of distinct histological origin. Br J Haematol 2011;154:477-81
125. Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, et al. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer 2011;117:5058-66
126. Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase II trial. Clin Lymphoma Myeloma Leuk 2011;11:462-6
127. Zaja F, De Luca S, Vitolo U, et al. Salvage treatment with lenalidomide and dexamethasone in patients with relapsed refractory mantle cell lymphoma: clinical results and modifications of angiogenic biomarkers. Haematologica 4 Nov 2011 [Epub ahead of print]
128. Nowakowski GS, Laplant B, Habermann TM, et al. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia 2011;25:1877-81
129. Vitolo U, Chiappella A, Carella AM, et al. Prospective, multicenter phase I - II pilot trial to evaluate efficacy and safety of lenalidomide plus rituximab-CHOP21 (LR-CHOP21) for elderly patients with untreated diffuse large B-cell lymphoma (DLBCL): interim analysis of the Intergruppo Italiano Linfomi (IIL) REAL07 study. Blood 2010;116:2871
130. Fehniger TA, Larson S, Trinkaus K, et al. A phase II multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood 2011;118(19):5119-25
131. Dueck G, Chua N, Prasad A, et al. Interim report of a phase II clinical trial of lenalidomide for T-cell non-Hodgkin lymphoma. Cancer 2010;116:4541-8
132. Seldin DC, Choufani EB, Dember LM, et al. Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis. Clin Lymphoma 2003;3:241-6 (Pubitemid 36416849)
133. Dispenzieri A, Lacy MQ, Rajkumar SV, et al. Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosis. Amyloid 2003;10:257-61 (Pubitemid 38117510)
134. Palladini G, Perfetti V, Perlini S, et al. The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood 2005;105:2949-51 (Pubitemid 40446290)
135. Wechalekar AD, Goodman HJ, Lachmann HJ, et al. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood 2007;109:457-64 (Pubitemid 46105938)
136. Dispenzieri A, Lacy MQ, Zeldenrust SR, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 2007;109:465-70 (Pubitemid 46105939)
137. Sanchorawala V, Wright DG, Rosenzweig M, et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase II trial. Blood 2007;109:492-6 (Pubitemid 46105943)
138. Sanchorawala V, Finn KT, Fennessey S, et al. Durable hematologic complete responses can be achieved with lenalidomide in AL amyloidosis. Blood 2010;116:1990-1
139. Moreau P, Jaccard A, Benboubker L, et al. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase I/II dose-escalation study. Blood 2010;116:4777-82
140. Patel J, Sloan JM, Shelton AC, et al. Melphalan, lenalidomide and dexamethasone combination therapy in patients with AL amyloidosis. Blood 2011;118:1260; abstract 2924
141. Gertz MA. Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011;86:180-6
142. Canepa L, Ballerini F, Varaldo R, et al. Thalidomide in agnogenic and secondary myelofibrosis. Br J Haematol 2001;115:313-15 (Pubitemid 34203493)
143. Barosi G, Elliott M, Canepa L, et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies. Leuk Lymphoma 2002;43:2301-7
144. Elliott MA, Mesa RA, Li CY, et al. Thalidomide treatment in myelofibrosis with myeloid metaplasia. Br J Haematol 2002;117:288-96 (Pubitemid 34451143)
145. Marchetti M, Barosi G, Balestri F, et al. Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial. J Clin Oncol 2004;22:424-31 (Pubitemid 41079770)
146. Thomas DA, Giles FJ, Albitar M, et al. Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer 2006;106:1974-84 (Pubitemid 43673213)
147. Mesa RA, Steensma DP, Pardanani A, et al. A phase II trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood 2003;101:2534-41 (Pubitemid 36857609)
148. Mesa RA, Elliott MA, Schroeder G, et al. Durable responses to thalidomide-based drug therapy for myelofibrosis with myeloid metaplasia. Mayo Clin Proc 2004;79:883-9 (Pubitemid 38879954)
149. Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 2006;108:1158-64 (Pubitemid 44232010)
150. Quintas-Cardama A, Kantarjian HM, Manshouri T, et al. Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol 2009;27:4760-6
151. Mesa RA, Yao X, Cripe LD, et al. Lenalidomide and prednisone for myelofibrosis: eastern Cooperative Oncology Group (ECOG) phase II trial E4903. Blood 2010;116:4436-8
152. Jabbour E, Thomas D, Kantarjian H, et al. Comparison of thalidomide and lenalidomide as therapy for myelofibrosis. Blood 2011;118:899-902
153. Tefferi A, Lasho TL, Mesa RA, et al. Lenalidomide therapy in del(5)(q31)- associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia 2007;21:1827-8 (Pubitemid 47086775)
154. Quintas-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010;115:3109-17
155. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2011;363:1117-27
156. Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 2009;27:4563-9
157. Begna KH, Mesa RA, Pardanani A, et al. A phase-II trial of low-dose pomalidomide in myelofibrosis. Leukemia 2011;25:301-4
158. Treon SP, Soumerai JD, Branagan AR, et al. Thalidomide and rituximab in Waldenstrom macroglobulinemia. Blood 2008;112:4452-7
159. Treon SP, Soumerai JD, Branagan AR, et al. Lenalidomide and rituximab in Waldenstrom's macroglobulinemia. Clin Cancer Res 2009;15:355-60
160. Gertz MA. Waldenstrom macroglobulinemia: 2011 update on diagnosis, risk stratification, and management. Am J Hematol 2011;86:411-16
161. Fehniger TA, Byrd JC, Marcucci G, et al. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood 2009;113:1002-5
162. Sekeres MA, Gundacker H, Lancet J, et al. A phase II study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: southwest Oncology Group Study S0605. Blood 2011;118:523-8
163. Blum W, Klisovic RB, Becker H, et al. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J Clin Oncol 2011;28:4919-25
164. Pollyea DA, Kohrt HE, Gallegos L, et al. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia 28 Oct 2011 [Epub ahead of print]
165. Dispenzieri A, Klein CJ, Mauermann ML. Lenalidomide therapy in a patient with POEMS syndrome. Blood 2007;110:1075-6 (Pubitemid 47267453)
166. Sethi S, Tageja N, Arabi H, et al. Lenalidomide therapy in a rare case of POEMS syndrome with kappa restriction. South Med J 2009;102:1092-3
167. Kuwabara S, Misawa S, Kanai K, et al. Thalidomide reduces serum VEGF levels and improves peripheral neuropathy in POEMS syndrome. J Neurol Neurosurg Psychiatry 2008;79:1255-7
168. Tomas JF, Giraldo P, Lecumberri R, et al. POEMS syndrome with severe neurological damage clinically recovered with Lenalidomide. Haematologica 2012;97:320-2
169. Bartlett JB, Michael A, Clarke IA, et al. Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer 2004;90:955-61 (Pubitemid 38495811)
170. Eisen T, Trefzer U, Hamilton A, et al. Results of a multicenter, randomized, double-blind phase II/III study of lenalidomide in the treatment of pretreated relapsed or refractory metastatic malignant melanoma. Cancer 2010;116:146-54
171. Hwu WJ, Knight RD, Patnana M, et al. Phase I safety study of lenalidomide and dacarbazine in patients with metastatic melanoma previously untreated with systemic chemotherapy. Melanoma Res 2010;20:501-6
172. Henry JY, Lu L, Adams M, et al. Lenalidomide enhances the anti-prostate cancer activity of docetaxel in vitro and in vivo. Prostate 3 Oct 2011 [Epub ahead of print]
173. Ain KB, Lee C, Williams KD. Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas. Thyroid 2007;17:663-70 (Pubitemid 47311556)
174. Ain KB, Lee C, Holbrook KM, et al. Phase II study of lenalidomide in distantly metastatic, rapidly progressive, and radioiodine-unresponsive thyroid carcinomas: preliminary results. J Clin Oncol 2008;26:abstract 6027
175. Carter JS, Geller MA, Judson PL, et al. A phase I study of lenalidomide in combination with liposomal doxorubicin in recurrent epithelial ovarian cancer. J Clin Oncol 2011;29:abstract e15545
176. Carter JS, Downs LS Jr. A prospective clinical trial of lenalidomide with topotecan in women with advanced epithelial ovarian carcinoma. Int J Clin Oncol 2011;16:666-70
177. Amato RJ, Hernandez-McClain J, Saxena S, et al. Lenalidomide therapy for metastatic renal cell carcinoma. Am J Clin Oncol 2008;31:244-9
178. Safran HS, Charpentier K, Kaubisch A, et al. Lenalidomide for advanced hepatocellular cancer (HCC) in patients progressing on or intolerant to sorafenib. J Clin Oncol 2011;29:abstract 4048
179. Infante JR, Jones SF, Bendell JC, et al. A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer. Eur J Cancer 2011;47:199-205
180. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516-20
181. Kapoor P, Gertz MA, Rajkumar V, et al. Survival outcome of young multiple myeloma (MM) patients in the era of novel therapies. Blood 2011;118:1273; abstract 2950
182. Hsu AK, Quach H, Tai T, et al. The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy. Blood 2011;117:1605-13
183. . Carbone E, Neri P, Mesuraca M, et al. HLA class I. NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood 2005;105:251-8 (Pubitemid 40053090)
184. Choi C, Witzens M, Bucur M, et al. Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma. Blood 2005;105:2132-4 (Pubitemid 40731802)
185. Carter CR, Feyler S, Smalle N, et al. Effect of combined dexamethasone/ lenalidomide therapy on NK cell-receptor levels in myeloma patients. Blood 2011;118:6465-6
186. Hsu AK, Quach H, Tai T, et al. Dexamethasone dose alters expression of NK activating receptors in vivo. Blood 2011;118:6466-8
187. Kurtin SE, List AF. Durable long-term responses in patients with myelodysplastic syndromes treated with lenalidomide. Clin Lymphoma Myeloma 2009;9:E10-13
188. Witzig TE, Wiernik PH, Moore T, et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol 2009;27:5404-9