Activity of IMiD® Agents

The IMiD® agents, lenalidomide and pomalidomide, have immunomodulatory properties that have been demonstrated in preclinical studies.1-6 IMiD® agents have been found to increase activation and proliferation of T cells, production of IL-2, and activity of CD8+ effector T cells.1-3 Stimulation and expression of natural killer (NK) cells, NK cell–mediated lysis via antibody-dependent cell-mediated cytotoxicity, and direct NK cell–mediated killing were also enhanced by IMiD® agents.2,4,5 In a preclinical study using multiple myeloma cell lines, lenalidomide enhanced immune response induced by checkpoint blockade between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1).6 These data and others have led Celgene to evaluate the role of lenalidomide and pomalidomide in combination with various agents in multiple myeloma.

In addition to immunomodulatory properties, IMiD® agents are hypothesized to have multiple mechanisms of action, including tumoricidal and antiangiogenic activity.7

Preclinical studies demonstrated increased anti-myeloma activity of IMiD agents in combination with dexamethasone and certain proteasome inhibitors and monoclonal antibodies.12-20

BORT, bortezomib; DARA, daratumumab; DEX, dexamathasone; ELO, elotuzumab; LEN, lenalidomide; MRZ, marizomib; OPZ, oprozomib; POM, pomalidomide.

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. Gandhi AK, et al. Br J Haematol. 2014;164:811-821.
  2. Seghal K, et al. Blood. 2015;125:4042-4051.
  3. Galustian C, et al. Expert Opin Biol Ther. 2004;4:1963-1970.
  4. Wu L, et al. Clin Cancer Res. 2008; 14:4650-4657.
  5. Lapalombella R, et al. Blood. 2008;112:5180-5189.
  6. Görgün G, et al. Clin Cancer Res. 2015;21:4607-4618.
  7. Quach H, et al. Leukemia. 2010;24:22-32.
  8. Lu G, et al. Science. 2014;343:305-309.
  9. Lopez-Girona A, et al. Leukemia. 2012;26:2326-2335.
  10. Kotla V, et al. J Hematol Oncol. 2009;12;2:36.
  11. Borrello I. Leuk Res. 2012;36:S3-S12.
  12. Imnovid (pomalidomide) [summary of product characteristics]. Uxbridge, UK: Celgene Europe; 2016.
  13. Rychak E, et al. Br J Haematol. 2016;172:889-901.
  14. Gandhi AK, et al. Curr Cancer Drug Targets. 2010;10:155-167.
  15. Celgene. Data on file (Report 8769-001).
  16. Chauhan D, et al. Blood. 2010;116:4906-4915.
  17. Das DS, et al. Br J Haematol. 2015;171:798-812.
  18. van der Veer MS, et al. Haematologica. 2011;96:284-290.
  19. Nijhof IS, et al. Clin Cancer Res. 2015;21:2802-2810.
  20. Boxhammer R, et al. Poster presented at ASCO 2015 [abstract 8588].