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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Position statement on the use of bortezomib in multiple myeloma
G J Morgan1, F E Davies, J D Cavenagh
1Haemato-Oncology Unit, Royal Marsden Hospital, London, UK.
Abstract:
Bortezomib (Velcade) is a boron containing molecule which reversibly inhibits the proteasome, an intracellular organelle which is central to the breakdown of ubiquinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate it is effective for the treatment of relapsed refractory myeloma, and a phase III trial comparing bortezomib to dexamethasone in second/third line treatment showed superiority in progression free and overall survival. It is administered intravenously in the outpatient setting on days 1, 4, 8 and 11 of a 21-day cycle and regular monitoring for side effects is essential. It is currently approved for the treatment of multiple myeloma patients who have received at least one prior therapy and who have already undergone or are unsuitable for transplantation. Given the strength of this data the UK Myeloma Forum and British Committee for Standards in Haematology believe that bortezomib should be available for prescription by UK haematologists according to its licensed indication in patients with relapsed myeloma.
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