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Updated: Jun 3, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Pomalidomide therapy for myeloma
Stephen Schey1, Karthik Ramasamy
1Kings College Hospital Foundation NHS Trust, Denmark Hill, London, UK. sschey@nhs.net
Introduction:
The Office of National Statistics (London, UK) has reported 4040 new patients in the year 2007, with an annual age standardized incidence rate of 4.8 per 100,000 population (range 4.7 - 5.0). Overall survival (OS) in the last decade has improved from 2 - 3 years to 7 - 8 years in the UK. The introduction of IMids for the treatment of myeloma has had a significant impact on outcomes in this life-threatening disease.
Areas Covered:
Pomalidomide, a thalidomide analogue, is a promising anti-myeloma agent with encouraging responses in relapsed/refractory myeloma patients. Pomalidomide has a potent anti-myeloma activity in vitro and in vivo, acting both directly on myeloma cells and on the cells in the bone marrow microenvironment. We have reviewed the chemistry and mechanisms of action of pomalidomide and the literature on pre-clinical and early Phase I and II clinical trials that demonstrates significant clinical efficacy in the relapsed setting and in lenalidomide refractory myeloma patients.
Expert Opinion:
Pomalidomide has shown significant activity in relapsed/refractory disease and is now being taken into Phase III trials in combination with dexamethasone. The exact place of pomalidomide in the management of myeloma, however, is evolving as more clinical experience is gained with this agent and further data published from clinical trials.
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