Lenalidomide is an IMiD® compound that has a multi-faceted mechanism of action in multiple myeloma that has been demonstrated in vitro and in vivo.1,2
Lenalidomide has immunomodulatory, tumoricidal, and antiangiogenic properties, and synergizes with dexamethasone to augment anti-myeloma activity.1
In vitro studies showed that lenalidomide induced myeloma cell death while also enhancing immune function, both of which are important mechanisms.1,3,4
Immunomodulatory properties of lenalidomide include the activation of CD4+ and CD8+ T cells and natural killer cells.1,5-7
Lenalidomide enhanced T cell proliferation and the downstream production of cytokines in vitro.4,6-8
Lenalidomide also increases the number of antigen-specific natural killer T cells, or NKT cells, which play a key role in immune surveillance.1,8-10
Lenalidomide activated NKT cells in vitro, which in turn, produced immunostimulatory cytokines.1,8,11,12 Lenalidomide also enhanced NKT cell activity in vivo.8,12
Lenalidomide activates NK cells, which leads to heightened immune surveillance—the ability of the immune system to both identify and eliminate tumor cells.13-16
Lenalidomide has tumoricidal effects on multiple myeloma.1 Preclinical findings showed that these apoptotic effects were specific to myeloma cell lines in vitro.17,18
Lenalidomide also demonstrates antiangiogenic properties.1 It has been shown to inhibit angiogenesis by reducing levels of VEGF, TNFa, and IL-6.1,19,20
In summary, IMiDs have a multifaceted mechanism of action by mediating myeloma cell death and enhancing immune function, and inhibiting angiogenesis.1,3,4
REVLIMID, an IMiD® compound with multiple mechanisms for Multiple Myeloma
Please see accompanying Important Safety Information and full Prescribing Information, including Boxed WARNINGS.
- REVLIMID [package insert]. Summit, NJ: Celgene Corporation.
- IMiDs, Available at: https://www.celgene.com/research-development/medical-innovation/imids/. Accessed June 28, 2016.
- Gandhi Ak, Kang J, Cappone 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(2):155-167.
- Borello I. Can we change the disease biology of multiple myeloma? Leuk Res. 2012;36 Suppl 1:S3-12.
- Gandhi AK, Kang J, Naziruddin S, et al. Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly.2006;30(7):849-858.
- 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(3):1222-1232.
- Haslett PA, Hanekom WA, Muller G, et al. Thalidomide and a thalidomide analogue drug costimulate virus-specific CD8+ T cells in vitro. J Infect Dis. 2003;187(6):946-955.
- Chang DH, Liu N, Klimek V, et al. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. 2006;108(2):618-621.
- Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol. 2002;14(2):165-171.
- Smyth MJ, Crowe NY, Hayakawa Y, et al. NKT cells – conductors of tumor immunity? Curr Opin Immunol. 2002;14(2):165-171.
- Song W, van der Vliet HJ, Tai YT, et al. Generation of antitumor invariant natural killer T cell lines in multiple myeloma and promotion of their functions via lenalidomide: a strategy for immunotherapy. Clin cancer Res. 2008;14(21):6955-6962.
- Ritcher J, Neparidze N, Zhang L, et al. Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma. 2013;121(3):423-430.
- Bianchi G, Richardson PG, Anderson KC. Promising therapies in multiple myeloma. 2015;126(3):300-310.
- Henry JY, Labarthe MC, Meyer B, et al. Enhanced cross-priming of naïve CD+8 T cells by dendritic cells treated by the IMiDs® immunomodulatory compounds lenalidomide and pomalidomide. 2013;139(#):377-385.
- Katodritou E, Terpos E, North J, et al. Tumor-primed natural killer cells from patients with multiple myeloma lyse autologous, NK-resistant, bone marrow-derived malignant plasma cells. AM J Hematol. 2011;86(12):967-973.
- Sharpe M, Mount N. Genetically modified T Cells in cancer therapy: opportunities and challenges. Dis Model Mech. 2015;8(4):337-350.
- 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.
- Tai YT, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. 2014;123(20):3128-3138.
- 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(7):1935-1946.
- Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. 2010;24(1):22-32.
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