Proposed Mechanism of Action
Pomalidomide is an oral immunomodulatory agent that, as demonstrated in vitro, inhibits proliferation and induces apoptosis of tumor cells, and inhibits proliferation of lenalidomide-resistant myeloma cells.1-3
In preclinical studies, pomalidomide has demonstrated direct tumoricidal and immunomodulatory effects, which are mediated in both myeloma and immune cells by targeting cereblon, a component of the E3 ubiquitin ligase complex.1-4 This interaction triggers proteasomal degredation of the transcription factors Ikaros and Aiolos,5,6 resulting in downregulation of the myeloma survival signals IRF4 and c-Myc5 and upregulation of the immunoregulatory molecule IL-2.3,6 Additionally, pomalidomide may have inhibitory effects on stromal-cell support in the bone marrow microenvironment, including inhibition of soluble protein production that supports myeloma cell growth and angiogenesis4,7
Pomalidomide Hypothesized Mechanism of Action
Pomalidomide is an IMiD® agent hypothesized to have tumoricidal and immunomodulatory effects in multiple myeloma.
Pomalidomide by Disease State
Pomalidomide in Multiple Myeloma
- Post Approval Research Multiple Myeloma Relapsed/refractory
View Trials Investigating Pomalidomide in Multiple Myeloma.Pomalidomide in Multiple Myeloma
Rationale for Clinical Development
For patients with multiple myeloma (MM) who are refractory to agents including bortezomib and lenalidomide, the prognosis is poor.8 Several ongoing studies are currently evaluating pomalidomide in combination with other agents, including bortezomib and marizomib, in patients with refractory or relapsed and refractory MM.
The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.
- Mitsiades N, et al. Blood. 2002;99:4525-4530.
- Verhelle D, et al. Cancer Res. 2007;67:746-755.
- Lopez-Girona A, et al. Leukemia. 2012;26:2326-2335.
- Quach H, et al. Leukemia. 2010;24:22-32.
- Bjorklund CC, et al. Blood Cancer J. 2015;5:e354.
- Gandhi AK, et al. Br J Haematol. 2014;164:811-821.
- Gupta D, et al. Leukemia. 2001;15:1950-1961
- Kumar SK, et al. Leukemia. 2012;26:149-157.