Pomalidomide

In the European Union, pomalidomide, in combination with bortezomib and dexamethasone, is indicated in the treatment of adults with multiple myeloma who have received at least one prior treatment regimen including lenalidomide; and in combination with dexamethasone is indicated in the treatment of adults with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy.{{cite web | title=Imnovid EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/imnovid-previously-pomalidomide-celgene | access-date=21 September 2020 | archive-date=27 October 2020 | archive-url=https://web.archive.org/web/20201027132039/https://www.ema.europa.eu/en/medicines/human/EPAR/imnovid-previously-pomalidomide-celgene | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

In the United States, pomalidomide is indicated, in combination with dexamethasone, for people with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy; and is indicated for people with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy (HAART) or in people with Kaposi sarcoma who are HIV-negative.{{cite web | title=Pomalidomide | website=National Cancer Institute | date=13 February 2013 | url=https://www.cancer.gov/about-cancer/treatment/drugs/pomalidomide | access-date=12 May 2023 | archive-date=15 January 2023 | archive-url=https://web.archive.org/web/20230115084913/https://www.cancer.gov/about-cancer/treatment/drugs/pomalidomide | url-status=live }} {{PD-notice}}{{cite web | title=FDA grants accelerated approval to pomalidomide for Kaposi sarcoma | website=U.S. Food and Drug Administration | date=15 May 2020 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pomalidomide-kaposi-sarcoma | access-date=12 May 2023 | archive-date=9 May 2023 | archive-url=https://web.archive.org/web/20230509061138/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pomalidomide-kaposi-sarcoma | url-status=live }} {{PD-notice}}{{cite press release | title=FDA approves pomalidomide for AIDS-related Kaposi sarcoma | website=National Cancer Institute | date=15 May 2020 | url=https://ccr.cancer.gov/news/article/fda-approves-pomalidomide-for-aids-related-kaposi-sarcoma | access-date=12 May 2023 | archive-date=8 May 2023 | archive-url=https://web.archive.org/web/20230508204356/https://ccr.cancer.gov/news/article/fda-approves-pomalidomide-for-aids-related-kaposi-sarcoma | url-status=live }}{{cite web | title=Cancer Accelerated Approvals | website=U.S. Food and Drug Administration | date=1 May 2023 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals | access-date=12 May 2023 | archive-date=27 April 2023 | archive-url=https://web.archive.org/web/20230427230841/https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals | url-status=live }}

The parent compound of pomalidomide, thalidomide, was originally discovered to inhibit angiogenesis in 1994.{{cite journal | vauthors = D'Amato RJ, Loughnan MS, Flynn E, Folkman J | title = Thalidomide is an inhibitor of angiogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 9 | pages = 4082–5 | date = April 1994 | pmid = 7513432 | pmc = 43727 | doi = 10.1073/pnas.91.9.4082 | bibcode = 1994PNAS...91.4082D | jstor = 2364596 | doi-access = free }} Based upon this discovery, thalidomide was taken into clinical trials for cancer, leading to its ultimate FDA approval for multiple myeloma.{{cite news| vauthors = Altman D |title=From Thalidomide to Pomalyst: Better Living Through Chemistry|url=https://www.damatolab.com/from-thalidomide-to-pomalyst}} 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.{{cite journal | vauthors = D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS | title = Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma | journal = Seminars in Oncology | volume = 28 | issue = 6 | pages = 597–601 | date = December 2001 | pmid = 11740816 | doi = 10.1016/S0093-7754(01)90031-4 }} This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo.{{cite journal | vauthors = Lentzsch S, Rogers MS, LeBlanc R, Birsner AE, Shah JH, Treston AM, Anderson KC, D'Amato RJ | title = S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice | journal = Cancer Research | volume = 62 | issue = 8 | pages = 2300–5 | date = April 2002 | pmid = 11956087 }}

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 inhibitors including rolipram and pentoxifylline do not inhibit myeloma cell growth or angiogenesis. Upregulation of interferon gamma, IL-2 and IL-10 as well as downregulation of IL-6 have been reported for pomalidomide. These changes may contribute to pomalidomide's anti-angiogenic and anti-myeloma activities.{{cn|date=February 2025}}

Like thalidomide, pomalidomide works as a cereblon E3 ligase modulator.{{Cite journal |vauthors=Asatsuma-Okumura T, Ito T, Handa H |date=October 2019 |title=Molecular mechanisms of cereblon-based drugs |journal=Pharmacology & Therapeutics |volume=202 |pages=132–139 |doi=10.1016/j.pharmthera.2019.06.004 |pmid=31202702 |doi-access=free}}

Pomalidomide can cause harm to unborn babies when administered during pregnancy.

Pomalidomide is present in the semen of people receiving the drug.

Phase I trial results showed tolerable side effects.{{cite journal | vauthors = Streetly MJ, Gyertson K, Daniel Y, Zeldis JB, Kazmi M, Schey SA | title = Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation | journal = British Journal of Haematology | volume = 141 | issue = 1 | pages = 41–51 | date = April 2008 | pmid = 18324965 | doi = 10.1111/j.1365-2141.2008.07013.x | s2cid = 37073246 }}

Phase II clinical trials for multiple myeloma and myelofibrosis reported 'promising results'.{{cite press release |title=Promising Results From 2 Trials Highlighting Pomalidomide Presented At ASH |publisher=Celgene |date=11 December 2008 |url=http://www.medicalnewstoday.com/releases/132590.php |access-date=28 October 2012 |archive-date=20 September 2018 |archive-url=https://web.archive.org/web/20180920152609/https://www.medicalnewstoday.com/releases/132590.php |url-status=live }}{{cite conference |url=https://ash.confex.com/ash/2008/webprogram/Paper13194.html |title=Pomalidomide Therapy in Anemic Patients with Myelofibrosis: Results from a Phase-2 Randomized Multicenter Study | vauthors = Tefferi A |date=8 December 2008 |conference=50th ASH Annual Meeting and Exposition |location=San Francisco |access-date=28 October 2012 |archive-date=20 September 2018 |archive-url=https://web.archive.org/web/20180920152602/https://ash.confex.com/ash/2008/webprogram/Paper13194.html |url-status=live }}

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 vs. dexamethasone alone.{{cite journal | vauthors = Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M | title = 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 | journal = The Lancet. Oncology | volume = 14 | issue = 11 | pages = 1055–1066 | date = September 2013 | pmid = 24007748 | doi = 10.1016/s1470-2045(13)70380-2 | hdl = 2318/150538 | s2cid = 4526729 | url = https://iris.unito.it/bitstream/2318/150538/1/1323531.pdf | hdl-access = free | access-date = 2 September 2019 | archive-date = 20 October 2021 | archive-url = https://web.archive.org/web/20211020032825/https://iris.unito.it/retrieve/handle/2318/150538/60224/1323531.pdf | url-status = live }}

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Category:Aromatic amines

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Category:Phthalimides