Open Access Articles- Top Results for Pomalidomide


Systematic (IUPAC) name
Clinical data
Trade names Imnovid, Pomalyst
Licence data EMA:Link, US FDA:link
  • US: X (Contraindicated)
Pharmacokinetic data
Protein binding 12–44%
Metabolism Hepatic (mostly CYP1A2 and CYP3A4 mediated; some minor contributions by CYP2C19 and CYP2D6)
Half-life 7.5 hours
Excretion Urine (73%), faeces (15%)
19171-19-8 7pxY
PubChem CID 134780
ChemSpider 118785 7pxN
Chemical data
Formula C13H11N3O4
273.24 g/mol
 14pxN (what is this?)  (verify)

Pomalidomide (INN, originally CC-4047 or 3-amino-thalidomide, trade name Pomalyst[1] in the US and Imnovid in Europe) is a derivative of thalidomide marketed by Celgene. It is anti-angiogenic and also acts as an immunomodulator. Pomalidomide was approved in February 2013 by the U.S. Food and Drug Administration (FDA) as a treatment for relapsed and refractory multiple myeloma.[2] It received a similar approval from the European Commission in August 2013.[3]

Origin and development

The parent compound of pomalidomide, thalidomide, was originally discovered to inhibit angiogenesis in 1994.[4] Based upon this discovery, thalidomide was taken into clinical trials for cancer, leading to its ultimate FDA approval for multiple myeloma.[5] Structure-activity studies revealed that amino substituted thalidomide had improved antitumor activity, which was due to its ability to directly inhibit both the tumor cell and vascular compartments of myeloma cancers.[6] This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo.[7]

Clinical trials

Phase I trial results showed tolerable side effects.[8]

Phase II clinical trials for multiple myeloma and myelofibrosis reported 'promising results'.[9][10]

Phase III results showed significant extension of progression-free survival, and overall survival (median 11.9 months vs. 7.8 months; P = 0.0002) in patients taking pomalidomide and dexamethasone v. dexamethasone alone.[11]


Pomalidomide directly inhibits angiogenesis and myeloma cell growth. This dual effect is central to its activity in myeloma, rather than other pathways such as TNF alpha inhibition, since potent TNF alpha inhibitors including rolipram and pentoxifylline do not inhibit myeloma cell growth nor angiogenesis.[6] Up regulation of Interferon gamma, IL-2 and IL-10 as well as down regulation of IL-6 have been reported for pomalidomide. These changes may contribute to pomalidomide's anti-angiogenic and anti-myeloma activities.

Pregnancy and sexual contact warnings

Because Pomalyst can cause harm to unborn babies when administered during pregnancy, women taking Pomalyst must not become pregnant. Women must produce two negative pregnancy tests and use contraception methods before beginning Pomalyst. Women must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning 4 weeks prior to initiating treatment with Pomalyst, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of Pomalyst therapy. Pomalyst is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing Pomalyst, even if they have undergone a successful vasectomy. Male patients taking Pomalyst must not donate sperm.

See also


  1. ^ "Pomalyst (Pomalidomide) Official Website". Celgene Corporation. Retrieved 2013-08-10. 
  2. ^ "Pomalyst (Pomalidomide) Approved By FDA For Relapsed And Refractory Multiple Myeloma". The Myeloma Beacon. Retrieved 2013-08-10. 
  3. ^ "Pomalidomide Approved In Europe For Relapsed And Refractory Multiple Myeloma". The Myeloma Beacon. Retrieved 2013-08-10. 
  4. ^ D'Amato, Robert J.; Loughnan, Michael S.; Flynn, Evelyn; Folkman, Judah (1994). "Thalidomide is an inhibitor of angiogenesis". Proceedings of the National Academy of Sciences of the United States of America 91 (9): 4082–5. Bibcode:1994PNAS...91.4082D. JSTOR 2364596. PMC 43727. PMID 7513432. doi:10.1073/pnas.91.9.4082. 
  5. ^
  6. ^ a b D'Amato, R; Lentzsch, S; Anderson, KC; Rogers, MS (2001). "Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma". Seminars in Oncology 28 (6): 597–601. PMID 11740816. doi:10.1016/S0093-7754(01)90031-4. 
  7. ^ Lentzsch, S; Rogers, MS; Leblanc, R; Birsner, AE; Shah, JH; Treston, AM; Anderson, KC; D'Amato, RJ (2002). "S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice". Cancer Research 62 (8): 2300–5. PMID 11956087. 
  8. ^ Streetly, Matthew J.; Gyertson, Kylie; Daniel, Yvonne; Zeldis, Jerome B.; Kazmi, Majid; Schey, Stephen A. (2008). "Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation". British Journal of Haematology 141 (1): 41–51. PMID 18324965. doi:10.1111/j.1365-2141.2008.07013.x. 
  9. ^ "Promising Results From 2 Trials Highlighting Pomalidomide Presented At ASH" (Press release). Celgene. December 11, 2008. Retrieved October 28, 2012. 
  10. ^ Tefferi, Ayalew (December 8, 2008). Pomalidomide Therapy in Anemic Patients with Myelofibrosis: Results from a Phase-2 Randomized Multicenter Study. 50th ASH Annual Meeting and Exposition. San Francisco. Retrieved October 28, 2012. 
  11. ^ San Miguel, J; Weisel, K; Moreau, P; Lacy, M; Song, K et al. (October 2014). "Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial". Lancet Oncology 14 (11): 1055–1066. PMID 24007748. 

External links