Lenalidomide: a synthetic compound with an evolving role in cancer management

References

• Dimopoulos M, Spencer A, Attal M et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357(21): 2123–2132.
   PubMed Web of Science ®Google Scholar
• Weber DM, Chen C, Niesvizky R et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357(21): 2133–2142.
   PubMed Web of Science ®Google Scholar
• Mitsiades CS, Mitsiades N. CC-5013 (Celgene). Curr Opin InvestigDrugs 2004; 5(6): 635–647.
   PubMedGoogle Scholar
• Teo SK, Oliver J, Harden D, Stirling D, Thoms S, Scheffler M. A phase I, single blind, placebo-controlled, ascending single oral dose, safety, tolerabilility and pharmakokinetic study of CDC-501, a novel immunomodullatory-oncologic agent, in health male subjects with a comparison of fed and fasted. Clin Pharm Ther 2002; 71(2): 93.
   Google Scholar
• Kotla V, Goel S, Nischal S et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009; 2: 36.
   PubMed Web of Science ®Google Scholar
• Muller GW, Chen R, Huang SY et al. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 1999; 9(11): 1625–1630.
   PubMed Web of Science ®Google Scholar
• Symeonidis A, Kourakli A, Katevas P et al. Immune function parameters at diagnosis in patients with myelodysplastic syn-dromes: correlation with the FAB classification and prognosis. Eur J Haematol 1991; 47(4): 277–281.
   PubMed Web of Science ®Google Scholar
• Chanan-Khan A, Miller KC, Musial L et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol 2006; 24(34): 5343–5349.
   PubMed Web of Science ®Google Scholar
• Lichtenstein A, Tu Y, Fady C, Vescio R, Berenson J. Interleukin-6inhibits apoptosis of malignant plasma cells. Cell Immunol 1995; 162(2): 248–255.
   PubMed Web of Science ®Google Scholar
• 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(1): 380–386.
   PubMed Web of Science ®Google Scholar
• LeBlanc R, Hideshima T, Catley LP et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood 2004; 103(5): 1787–190.
   PubMed Web of Science ®Google Scholar
• 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 Thl -type immunity. J Immunol 2002; 168(10): 4914–4919.
   PubMed Web of Science ®Google Scholar
• Stirling D. Thalidomide: a novel template for anticancer drugs. Semin Oncol 2001; 28(6): 602–606.
   PubMed Web of Science ®Google Scholar
• Davies FE, Raje N, Hideshima T et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cyto-toxicity in multiple myeloma. Blood 2001; 98(1): 210–216.
   PubMed Web of Science ®Google Scholar
• Hayashi T, Hideshima T, Akiyama M et al. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol 2005; 128(2): 192–203.
   PubMed Web of Science ®Google Scholar
• Bartlett JB. Lenalidomide enhances tumor killing in vitro during ADCC mediated by Trastuzumab, Cetuximab, and Rituximab. J Clin Oncol 2007; 25(18S): 3023.
   Google Scholar
• 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(12): 1950–1961.
   PubMed Web of Science ®Google Scholar
• Giagounidis AA, Germing U, Haase S et al. Clinical, morpholo-gical, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 2004; 18(1): 113–119.
   PubMed Web of Science ®Google Scholar
• Buesche G. Anti-angiogenic in vivo effect of lenalidomide in MDS with del(5q) chromosome abnormality. Oral Abstract Session ASCO 2007 2007.
   Google Scholar
• 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(2): 746–755.
   PubMed Web of Science ®Google Scholar
• 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(9): 2943–2950.
   PubMed Web of Science ®Google Scholar
• Chanan-Khan A. Pro-Apoptotic effect of Lenalidomide in patients with Chronic Lymphocytic Leukemia is possibly mediated through interruption of Phosphatidylinositol pathway. Blood (ASH annual meeting abstracts) 2006,108.
   Google Scholar
• 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(27): 11406–11411.
   PubMed Web of Science ®Google Scholar
• Ebert BL, Galili N, Tamayo P et al. An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome. PLoS Med 2008; 5(2): e35.
   PubMed Web of Science ®Google Scholar
• List A, Kurtin S, Roe DJ et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005; 352(6): 549–557.
   PubMed Web of Science ®Google Scholar
• List A, Dewald G, Bennett J et al Lenalidomide in the myelodys-plastic syndrome with chromosome 5q deletion. N Engl J Med 2006; 355(14): 1456–1465.
   PubMed Web of Science ®Google Scholar
• List A, Dewald G, Bennett J. Clinical benefit from 2 phase II trials evaluating lenalidomide (Revlimid) in lower-risk myelodysplastic syndrome patients with or without del 5q cytoenetic abnormalities (abstract). European Hematology Association 11th Congress Proceedings; 2006 June 15–18; Amsterdam, The Netherlands. EHA, Abstract 1032.
   Google Scholar
• List A. Treatment and prognosis of the myelodysplastic syn-dromes. Proceeding of 9th International Symposium on MDS; May 2007; Florence, Italy.
   Google Scholar
• Ades L, Boehrer S, Prebet T et al. Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syn-dromes with 5q deletion: results of a phase 2 study. Blood 2009; 113(17): 3947–3952.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Issa JP, Rosenfeld CS et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006; 106(8): 1794–1803.
   PubMed Web of Science ®Google Scholar
• Silverman LR, Demakos EP, Peterson BL et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002; 20(10): 2429–2440.
   PubMed Web of Science ®Google Scholar
• Jondsova A, Neuwirtova R, Cerro& J et al. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol 1998; 100(2): 304–309.
   PubMed Web of Science ®Google Scholar
• Molldrem JJ, Caples M, Mavroudis D, Plante M, Young NS, Barrett A.J. Antithymocyte globulin for patients with myelodys-plastic syndrome. Br J Haematol 1997; 99(3): 699–705.
   PubMed Web of Science ®Google Scholar
• Rajkumar SV, Hayman SR, Lacy MQ et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106(13): 4050–4053.
   PubMed Web of Science ®Google Scholar
• Rajkumar SV, Jacobus S, Callender N et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group (abstract). J Clin Oncol 2007; 25: 968s.
   Google Scholar
• Niesvizky R, Jayabalan DS, Christos Pi et al. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]klexamethasone) combi-nation therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood 2008; 111(3): 1101–1109.
   PubMed Web of Science ®Google Scholar
• Wang M, Delasalle K, Giralt S, Alexanian R. Rapid control of previously untreated multiple myeloma with bortezomib-lenalido-mide-dexamethasone (BLD). Blood 2007; 110: (Abstract no. 3611).
   Web of Science ®Google Scholar
• Richardson P, Hagannath S, Raje N et al. Lenalidomide, bortezomib and dexamethasone (RevNel/Dex) as front-line therapy for patients with multiple myeloma (MML): preliminary results of a phase 1/2 study. Blood 2007; 110 (Abstract no. 187).
   Web of Science ®Google Scholar
• 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(28): 4459–4465.
   PubMed Web of Science ®Google Scholar
• 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(4): 772–778.
   PubMed Web of Science ®Google Scholar
• Richardson PG, Blood E, Mitsiades CS et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 108(10): 3458–3464.
   PubMed Web of Science ®Google Scholar
• 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/dezamethasone (MM009/010 sub-analysis). Blood 2007; 110: (Abstract no. 2712).
   PubMed Web of Science ®Google Scholar
• Knop S, Gerecke C, Topp MS et al. Lenalidomide, adriamycin and dexamethasone chemotherapy (RAD) is safe and effective in treatment of relapsed multiple myeloma-First results of a German multicenter Phase I/II Trial. Blood 2006; 108: (Abstract no. 408).
   Web of Science ®Google Scholar
• Morgan GJ, Schey SA, Wu P et al. Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients. Br J Haematol 2007; 137(3): 268–269.
   PubMed Web of Science ®Google Scholar
• Baz R, Walker E, Karam MA et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refrac-tory multiple myeloma: safety and efficacy. Ann Oncol 2006; 17(12): 1766–1771.
   PubMed Web of Science ®Google Scholar
• Chanan-Khan A, Porter CW. Immunomodulating drugs for chronic lymphocytic leukaemia. Lancet Oncol 2006; 7(6): 480–488.
   PubMed Web of Science ®Google Scholar
• Richardson P, Jagannath S, Raje N et al. Lenalidomid, bortezomib and dexamethasone (RevNel/Dex) in patients with relapsed or relapsed/refractory multiple myeloma (MM): preliminary results of a phase II study. Blood 2007; 110: (Abstract no. 2714).
   Web of Science ®Google Scholar
• Richardson PG, Jagannath S, Avigan DE et al. Lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): final results of a multicenter phase 1 trial. Blood 2006; 108: (Abstract no. 405).
   PubMed Web of Science ®Google Scholar
• Ferrajoli A, Lee BN, Schlette El et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 2008; 111(11): 5291–5297.
   PubMed Web of Science ®Google Scholar
• Ferrajoli A, O'Brien S, Wierda W et al. Lenalidomide as initial treatment of elderly patients with chronic lymphocytic leukemia (CLL). Blood 2008,112, 23.
   Web of Science ®Google Scholar
• Chen C, Paul H, Xu W et al. A phase II study of lenalidomide in previously untreated, symptomactic chronic lymphocytic leukemia (CLL). Blood 2008; 112: 23.
   Web of Science ®Google Scholar
• Andritsos LA, Johnson AJ, Lozanski G et al. Higher doses of lenalidomide are associated with unacceptable toxicity including life-threatening tumor flare in patients with chronic lymphocytic leukemia. J Clin Oncol 2008; 26(15): 2519–2525.
   PubMed Web of Science ®Google Scholar
• Arana-Yi C, Quintas-Cardama A, Giles F et al. Advances in the therapy of chronic idiopathic myelofibrosis. Oncologist 2006; 11(8): 929–943.
   PubMed Web of Science ®Google Scholar
• Tefferi A, Cortes J, Verstovsek S et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. 2006; 108(4): 1158–1164.
   PubMed Web of Science ®Google Scholar
• Treon SP, Soumerai JD, Branagan AR et al. Lenalidomide and rituximab in Waldenstrom's macroglobulinemia. Clin Cancer Res 2009; 15(1): 355–360.
   PubMed Web of Science ®Google Scholar
• Treon SP, Soumerai JD, Branagan AR et al. Thalidomide and rituximab in Waldenstrom macroglobulinemia. Blood 2008; 112(12): 4452–4457.
   PubMed Web of Science ®Google Scholar
• Wiernik PH, Lossos IS, Tuscano JM et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 2008; 26(30): 4952–4957.
   PubMed Web of Science ®Google Scholar
• Goy A, Younes A, McLaughlin P et al. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol 2005; 23(4): 667–675.
   PubMed Web of Science ®Google Scholar
• Fossä A, Santoro A, Hiddemann W et al. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 1999; 17(12): 3786–3792.
   PubMed Web of Science ®Google Scholar
• Coiffier B, Haioun C, Ketterer N et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase 11 study. Blood 1998; 92(6): 1927–1932.
   PubMed Web of Science ®Google Scholar
• 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(3): 344–349.
   PubMed Web of Science ®Google Scholar
• Fisher RI, Bernstein SH, Kahl BS et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2006; 24(30): 4867–4874.
   PubMed Web of Science ®Google Scholar
• Witzig TE, Geyer SM, Ghobrial I et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 2005; 23(23): 5347–5356.
   PubMed Web of Science ®Google Scholar
• Wang M, Fayad L, Hagemeister F. A phase I/II study of lenalidomide in combination with rituximab in relapsed/refractory mantle cell lymphoma with early evidence of efficacy. J Clinic Oncol 2007; 25: 448s ( suppl; abstr 8030).
   Google Scholar
• 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(2): 465–470.
   PubMed Web of Science ®Google Scholar
• Sanchorawala V, Wright DG, Rosenzweig M et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 2007; 109(2): 492–496.
   PubMed Web of Science ®Google Scholar
• Miller AA, Case D, Harmon M et al. Phase I study of lenalidomide in solid tumors. J Thorac Oncol 2007; 2(5): 445–449.
   PubMed Web of Science ®Google Scholar
• Dahut WL, Aragon-Ching JB, Woo S et al. Phase I study of oral lenalidomide in patients with refractory metastatic cancer. J Clin Pharmacol 2009; 49(6): 650–660.
   PubMed Web of Science ®Google Scholar
• Fine HA, Figg WD, Jaeckle K et al. Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 2000; 18(4): 708–715.
   PubMed Web of Science ®Google Scholar
• Fine HA, Kim L, Albert PS et al. A phase I trial of lenalidomide inpatients with recurrent primary central nervous system tumors. Clin Cancer Res 2007; 13(23): 7101–7106.
   PubMed Web of Science ®Google Scholar
• Pyrhonen S, Salminen E, Ruutu M et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 1999; 17(9): 2859–2867.
   PubMed Web of Science ®Google Scholar
• Dexeus FH, Logothetis CJ, Sella A et al. Circadian infusion of floxuridine in patients with metastatic renal cell carcinoma. J Urol 1991; 146(3): 709–713.
   PubMed Web of Science ®Google Scholar
• Mertens WC, Eisenhauer EA, Moore M et al. Gemcitabine in advanced renal cell carcinoma. A phase II study of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 1993; 4(4): 331–332.
   Google Scholar
• Gordon MS, Manola J, Fairclough D et al. Low dose interferon a2b (IFN) + thalidomide in patients with previously untreated renal cell cancer (RCC). Improvement in progression-free survival but not quality of life or overall survival. A phase Ili study of the Eastern Cooperative Oncology Group (E2898) (abstract). Proc Am Soc Clin Oncol 2004; 22: 386s.
   Web of Science ®Google Scholar
• Choueiri TK, Dreicer R, Rini BI et al. Phase II study of lenalidomide in patients with metastatic renal cell carcinoma. Cancer 2006; 107(11): 2609–2616.
   PubMed Web of Science ®Google Scholar
• Amato RJ, Hernandez-McClain J, Saxena S, Khan M. Lenalidomide therapy for metastatic renal cell carcinoma. Am J Clin Oncol 2008; 31(3): 244–249.
   PubMed Web of Science ®Google Scholar
• Zhang L, Conejo-Garcia JR, Katsaros D et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348: 203–213.
   PubMed Web of Science ®Google Scholar
• Zhang MM, Chan JK, Husain A, Guo HY, Teng NN. Safety and efficacy of lenalidomide (Revlimid) in recurrent ovarian and primary peritoneal carcinoma. Gynecol Oncol 2007; 105(1): 194–198.
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Kastritis E, Rajkumar SV. Treatment of plasma cell dyscrasias with lenalidomide. Leukemia 2008; 22(7): 1343–1353.
   PubMed Web of Science ®Google Scholar
• Zonder JA, Barlogie B, Dune BG, McCoy J, Crowley J, Hussein MA. Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. Blood 2006; 108(1): 403.
   PubMed Web of Science ®Google Scholar