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Currently, you can access the following clinical trials being conducted worldwide:
Lenalidomide is an oral, small-molecule immunomodulatory agent that directly induces tumor-cell killing and enhances immune function in preclinical studies.1,2
Lenalidomide co-opts cereblon, a component of the E3 ubiquitin ligase complex, leading to direct tumoricidal and immunomodulatory effects.3-6?Preclinical studies have demonstrated increased activity of lenalidomide in combination with rituximab, an anti-CD20 monoclonal antibody that has been leveraged in the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia.7-12?Combinations of lenalidomide and rituximab are being investigated for the treatment of NHL subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma.13-15
Haploinsufficiency, caused when only 1 copy of a gene is present, is hypothesized to drive pathogenesis of del(5q) myelodysplastic syndromes (MDS)16-18?and may underlie the specific activity of lenalidomide.19?In myeloid cell lines, haploinsufficiency increases the sensitivity of del5q MDS cells to lenalidomide-mediated degradation of casein kinase 1A1 (CSNK1A1), a gene located in the deleted region of chromosome 5 in del(5q) MDS.20,21
Preclinical and correlative studies in MDS cells suggest that in non-del(5q) MDS, the effects of lenalidomide on cellular progenitors and the microenvironment work together to promote normal erythropoiesis through expansion of progenitor populations,1,22?reduction in proinflammatory cytokines,22?and reduction of marrow microvessel?density.22
In preclinical studies, lenalidomide has demonstrated direct tumoricidal and immunomodulatory effects, which are mediated in both myeloma and immune cells by co-opting cereblon, a component of the E3 ubiquitin ligase complex.2-6?This interaction triggers proteasome degredation of transcription factors Ikaros and Aiolos, resulting in downregulation of myeloma survival signals, IRF4 and c-Myc, and upregulation of immunoregulatory molecule IL-2.4,6,23
Lenalidomide Hypothesized Mechanism of Action in Multiple Myeloma
Lenalidomide is an IMiD?agent shown in vitro to have direct tumoricidal and immunomodulatory effects in lymphoma, multiple myeloma, and myelodysplastic syndromes.