{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:31:34Z","timestamp":1791322294541,"version":"4.3.1"},"reference-count":83,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,3,20]]},"abstract":"<jats:p>Lenalidomide is a novel anticancer agent that has made a major impact in the treatment of patients with B-cell malignancies. A more potent analog of thalidomide, lenalidomide was developed to enhance immunomodulatory properties with improved safety profile. Its antitumor activity seems mediated through modulation of both the cytokine and cellular tumor cell microenvironment. Preclinical as well as clinical observations demonstrate that lenalidomide downregulates production of various critical prosurvival cytokines in the tumor microenvironment while concurrently promoting activation of T- and natural killer (NK) cell-mediated antitumor response. Early clinical investigations noted its efficacy in relapsed and\/or refractory multiple myeloma patients. Subsequently, larger randomized studies confirmed the clinical benefit of lenalidomide when added to dexamethasone compared with dexamethasone alone in previously treated myeloma patients resulting in its recent approval by the US Food and Drug Administration. Consequently, the role of lenalidomide in other B-cell malignancies has been investigated, with impressive results in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. This review summarizes the data from various clinical investigations and highlights the impact of lenalidomide in the management of patients with B-cell malignancies.<\/jats:p>","DOI":"10.1200\/jco.2007.14.5367","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T04:45:45Z","timestamp":1203482745000},"page":"1544-1552","source":"Crossref","is-referenced-by-count":153,"title":["Lenalidomide for the Treatment of B-Cell Malignancies"],"prefix":"10.1200","volume":"26","author":[{"given":"Asher A.","family":"Chanan-Khan","sequence":"first","affiliation":[{"name":"From the Roswell Park Cancer Institute, Buffalo, NY; and Georgetown University Hospital, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Cheson","sequence":"additional","affiliation":[{"name":"From the Roswell Park Cancer Institute, Buffalo, NY; and Georgetown University Hospital, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911183412102"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.03.139"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.0221"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1323"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.1.4.675"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2005.01.002"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600607"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402745"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(06)70723-9"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.2174\/1568008033340207"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2005.10.001"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Chanan-Khan A, Padmanabhan S, Miller K, et al: In vivo evaluation of immunomodulating effects of lenalidomide on tumor cell microenvironment as a possible underlying mechanism of the antitumor effects observed in patients with chronic lymphocytic leukemia (CLL). Blood 106,2005, (abstr 2975a)","DOI":"10.1182\/blood.V106.11.2975.2975"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2006.01.010"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Chanan-Khan A, Ersing N, Krammer D, et al: Pro-apoptotic effect of lenalidomide in patients with chronic lymphocytic leukemia is possibly mediated through interruption of the phosphatidylinositol pathway. Blood 108,2006, (abstr 2102a)","DOI":"10.1182\/blood.V108.11.2102.2102"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"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 163:380,1999-386,","DOI":"10.4049\/jimmunol.163.1.380"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4184"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.048496"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05286.x"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Padmanabhan S, Ersing N, Wallace P, et al: First clinical evidence of in vivo Natural Killer (NK) cell modulation in chronic lymphocytic leukemia (CLL) patients treated with lenalidomide. Blood 108,2006, (abstr 2109a)","DOI":"10.1182\/blood.V108.11.2109.2109"},{"key":"R20","unstructured":"Mitsiades CS, Mitsiades N: CC-5013 (Celgene). Curr Opin Investig Drugs 5:635,2004-647,"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0996"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-015909"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Weber D, Chen C, Niesvizky R, et al: Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009). J Clin Oncol 24:427s,2006, (suppl; abstr 7521)","DOI":"10.1200\/jco.2006.24.18_suppl.7521"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"Dimopoulos MA, Spenser A, Attal M, et al: Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): Results of a phase 3 study (MM-010). Proc Am Soc Hematol 106:6,2005,","DOI":"10.1182\/blood.V106.11.6.6"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.1648"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Stadtmauer E, Weber D, Dimopolous M, et al: Lenalidomide in combination with dexamethasone is more effective than dexamethasone at first relapse in relapsed multiple myeloma. Proc Am Soc Hematol 2005 (abstr 3522)","DOI":"10.1182\/blood.V108.11.3552.3552"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2817"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.8527"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.3463"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl313"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06538.x"},{"key":"R32","doi-asserted-by":"crossref","unstructured":"Richardson P, Jagannath S, Avigan D, et al: Lenalidomide plus bortezomib (Rev-Vel) in relapsed and\/or refractory multiple myeloma (MM): Final results of a multicenter phase 1 trial. Proc Am Soc Hematol 2006 (abstr 405)","DOI":"10.1182\/blood.V108.11.405.405"},{"key":"R33","unstructured":"Richardson PG, Jagannath S, Raje N, et al: Phase 2 study of Rev\/Vel\/Dex in relapsed \/refractory multiple myeloma. Haematologica 2007 (abstr PO-660)"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0796"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1258"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.12.051"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.3109\/10428199309086993"},{"key":"R38","unstructured":"Reed JC: Bcl-2 family proteins: Regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol 34:9,1997-19,"},{"key":"R39","unstructured":"Thomas A, El Rouby S, Reed JC, et al: Drug-induced apoptosis in B-cell chronic lymphocytic leukemia: Relationship between p53 gene mutation and bcl-2\/bax proteins in drug resistance. Oncogene 12:1055,1996-1062,"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1997.17"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.3109\/10428199509059618"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Orsini E, Fao R: Cytokines and soluble molecules in CLL, in Fauget G (ed): Chronic Lymphocytic Leukemia. Totowa, NJ, Humana Press, pp 123,2005-142","DOI":"10.1007\/978-1-59259-412-2_6"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402467"},{"key":"R44","unstructured":"Hoffbrand AV, Panayiotidis P, Reittie J, et al: Autocrine and paracrine growth loops in chronic lymphocytic leukemia. Semin Hematol 30:306,1993-317,"},{"key":"R45","doi-asserted-by":"crossref","unstructured":"Reittie JE, Yong KL, Panayiotidis P, et al: Interleukin-6 inhibits apoptosis and tumour necrosis factor induced proliferation of B-chronic lymphocytic leukaemia. Leuk Lymphoma 22:83,1996-90, follow 186, color plate VI,","DOI":"10.3109\/10428199609051732"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(02)01046-9"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1385\/MO:22:3:291"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830300203"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V63.2.305.305"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-005-0675-4"},{"key":"R51","doi-asserted-by":"crossref","unstructured":"Johnston PB, Kay N: Pathogenesis of impaired cellular immune fucntion in CLL, in Faguet G (ed): Chronic Lymphocytic Leukemia: Molecular Genetics, Biology, Diagnosis, and Management. Totowa, NJ, Humana Press, 2004","DOI":"10.1007\/978-1-59259-412-2_5"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24176"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1038\/nm0997-984"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.11.4297"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0669"},{"key":"R56","unstructured":"Kay N, Geyer S, Yaqoob I, et al: Thalidomide treatment in chronic lymphocytic leukemia (CLL): A north central cancer treatment group (NCCTG) study. Blood 102:5162,2003,"},{"key":"R57","doi-asserted-by":"crossref","unstructured":"Furman R, Leonard J, Allen S, et al: Thalidomide alone or in combination with fludarbabine are effective treatments for patients with fludarabine-relapsed and refractory CLL. J Clin Oncol 23:595s,2005, (suppl; abstr 6640)","DOI":"10.1200\/jco.2005.23.16_suppl.6640"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.0401"},{"key":"R59","unstructured":"Ferrajoli A, O'Brien S, Faderl SH, et al: Therapy with lenalidomide in patients with relapsed chronic lymphocytic leukemia. Leuk Lymph 48:S160,2007,"},{"key":"R60","doi-asserted-by":"crossref","unstructured":"DiMiceli L, Miller K, Rickert M, et al: Characterization of IMiDs (immunomodulating agents) induced \u201cflare reaction\u201d in patients with chronic lymphocytic leukemia (CLL) and correlation with changes in serum cytokine levels. Blood 106,2005, (abstr 5049)","DOI":"10.1182\/blood.V106.11.5049.5049"},{"key":"R62","doi-asserted-by":"crossref","unstructured":"Moutouh-de Parseval LA, Weiss L, DeLap RJ, et al: Tumor lysis syndrome\/tumor flare reaction in lenalidomide-treated chronic lymphocytic leukemia. J Clin Oncol 25:246s,2007, (suppl; abstr 5047)","DOI":"10.1200\/JCO.2007.14.2141"},{"key":"R63","unstructured":"Chanan-Khan MK, Whitworth A, Lawrence D, et al: Clinical activity of lenalidomide in relapsed or refractory chronic lymphocytic leukemia (CLL) patients: Updated results of a phase II clinical trial. Leuk Lymph 48:S166,2007,"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V110.11.754.754"},{"key":"R65","doi-asserted-by":"crossref","unstructured":"Chanan-Khan A, Czuczman M, Padmanabhan S, et al: Clinical efficacy of lenalidomide in fludarabine-refractory chronic lymphocytic leukemia patients. Blood 24:5343,2006-5349,","DOI":"10.1200\/JCO.2005.05.0401"},{"key":"R66","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V110.11.2042.2042"},{"key":"R67","doi-asserted-by":"crossref","unstructured":"Corral L, Zhu D, Wang Y, et al: The IMiDs immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce growth arrest and apoptosis in NHL tumor cells in vitro. Blood 2006 (abstr 2388)","DOI":"10.1182\/blood.V108.11.2388.2388"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V108.11.3714.3714"},{"key":"R69","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0577"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2882"},{"key":"R71","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1091"},{"key":"R72","doi-asserted-by":"crossref","unstructured":"Wang M, Fayad L, Hagemeister F, et al: A phase I\/II study of lenalidomide (Len) in combination with rituximab (R) in relapsed\/refractory mantle cell lymphoma (MCL) with early evidence of efficacy. J Clin Oncol 25:18s,2007, (suppl; abstr 7522)","DOI":"10.1200\/jco.2007.25.18_suppl.8030"},{"key":"R73","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.050"},{"key":"R74","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.108"},{"key":"R75","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.16.3596"},{"key":"R76","doi-asserted-by":"publisher","DOI":"10.1080\/1042819021000006303"},{"key":"R77","doi-asserted-by":"crossref","unstructured":"Treon SP, Patterson CJ, Hunter ZR, et al: Phase II Study of CC-5013 (Revlimid) and Rituximab in Waldenstr\u00f6m's macroglobulinemia: Preliminary Safety and Efficacy Results. Blood 2006 (abstr 2443)","DOI":"10.1182\/blood.V106.11.2443.2443"},{"key":"R78","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-030544"},{"key":"R79","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc053530"},{"key":"R80","doi-asserted-by":"publisher","DOI":"10.1080\/10428190600799631"},{"key":"R81","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06698.x"},{"key":"R82","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007309563"},{"key":"R83","unstructured":"Knop S, Gerecke C, Topp M, et al: RAD (Revlimid, adriamycin, dexamethasone) is a new treatment for relapsed multiple myeloma. Haematologica 2007 (abstr PO-658)"},{"key":"R84","doi-asserted-by":"crossref","unstructured":"Wiernik PH, Lossos IS, Tuscano J, et al: Preliminary results from a phase II study of lenalidomide oral monotherapy in relapsed\/refractory aggressive non-Hodgkin lymphoma. J Clin Oncol 25:457s,2007, (suppl; abstr 8066)","DOI":"10.1200\/jco.2007.25.18_suppl.8066"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2007.14.5367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T15:14:19Z","timestamp":1684250059000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2007.14.5367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,20]]},"references-count":83,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,3,20]]}},"alternative-id":["10.1200\/JCO.2007.14.5367"],"URL":"https:\/\/doi.org\/10.1200\/jco.2007.14.5367","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,20]]}}}