Pomalidomide (IMiD® Agent)

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 been shown to exhibit tumoricidal, immunomodulatory, and anti-stromal support activity.4

  • Pomalidomide may exert direct anti-myeloma effects by inducing cell-cycle arrest and apoptosis, including that of lenalidomide-resistant cells, through the activation of tumor suppressor genes, such as p21, and inhibition of oncogenes, including IRF4 1-3,5-7
  • Pomalidomide may enhance T- and natural killer (NK)-cell–mediated immunity and inhibit production of pro-inflammatory cytokines by monocytes2,8-11
  • 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 angiogenesis8,12,13

IFN, interferon; IL, interleukin; IRF4, interferon regulatory factor 4; MM, multiple myeloma; NK, natural killer; TNF, tumor necrosis factor; TSG, tumor suppressor gene; VEGF, vascular endothelial growth factor.

Pomalidomide by Disease State

Pomalidomide in Multiple Myeloma

  • Post Approval Research Multiple Myeloma Relapsed/refractory

Rationale for Clinical Development

For patients with multiple myeloma (MM) who are refractory to agents including bortezomib and lenalidomide, the prognosis is poor.14 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.

References

  1. Mitsiades N, et al. Blood. 2002;99:4525-4530.
  2. Verhelle D, et al. Cancer Res. 2007;67:746-755.
  3. Lopez-Girona A, et al. Leukemia. 2012;26:2326-2335.
  4. Quach H, et al. Leukemia. 2010;24:22-32.
  5. Rychak E, et al. Clin Lymphoma Myeloma Leuk. 2011;96:s126 [poster presentation].
  6. Hideshima T, et al. Blood. 2000;96:2943-2950.
  7. Escoubet-Lozach L, et al. Cancer Res. 2009;69:7347-7356.
  8. Corral LG, et al. J Immunol. 1999;163:380-386.
  9. Henry JY, et al. Immunology. 2013;139:377-385.
  10. Hayashi T, et al. Br J Haematol. 2005;128:192-203.
  11. Davies FE, et al. Blood. 2001;98:210-216.
  12. Gupta D, et al. Leukemia. 2001;15:1950-1961
  13. Hideshima T, et al. Blood. 2000;96:2943-2950.
  14. Kumar SK, et al. Leukemia. 2012;26:149-157.