Multiple myeloma (MM) is a haematological disease characterized by plasma cells proliferation in bone marrow associated with damage of organs – mainly kidneys and bones. Previous therapies ...significantly extended the survival of patients, but still relapse is 100%. In February 2013, in USA, the Food and Drug Administration (FDA) introduced to therapy a new immunomodulatory drug – pomalidomide. In European Union this drug under the name IMNOVID was registered in August 2013. The authors review the mechanisms of action, pharmacokinetic and clinical properties of pomalidomide. The data discussed in this article come from publications on clinical trials I, II and III phase. It seems this drug may be a breakthrough in the treatment of MM.
Molecular background of complex biological effects of immunomodulatory drugs (IMiDs) thalidomide, lenalidomide and pomalidomide has been largely unknown. Recently, a role of cereblon (CRBN) as a ...common molecular target for IMiDs and protein crucial for teratogenicity of thalidomide, as well as anti-proliferative, anti-angiogenic and immunomodulatory effects of IMiDs, has been elucidated. In this paper we review published pre-clinical and clinical data on the significance of CRBN expression. Moreover, we discuss perspectives on clinical application of evaluation of CRBN for individualization and monitoring of IMiDs-based therapy.
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Le pomalidomide dans le myélome multiple Fouquet, G.; Macro, M.; Decaux, O. ...
La revue de medecine interne,
September 2015, 2015-09-00, Volume:
36, Issue:
9
Journal Article
Peer reviewed
Auparavant caractérisé par un très mauvais pronostic, le myélome multiple (MM) est aujourd’hui compatible avec une survie prolongée, grâce aux progrès majeurs liés à l’utilisation des « nouveaux ...agents » : les inhibiteurs du protéasome (dont le bortézomib) et les IMiD (immunomodulateurs, tels que la thalidomide ou le lénalidomide). Cependant, la grande majorité des patients – si ce n’est tous les patients – vont rechuter et devenir éventuellement réfractaires à tous les traitements disponibles, y compris ces nouveaux agents. Il reste donc des progrès à faire dans cette situation, notamment via le développement de la prochaine génération d’inhibiteurs du protéasome et d’IMiD, et le développement de nouvelles classes thérapeutiques. Cette revue se concentre sur le pomalidomide, un IMiD de nouvelle génération dont l’utilisation a été récemment approuvée par la Food and Drug Administration (FDA) aux États-Unis et l’European Medicines Agency (EMA) en Europe, pour les patients présentant un myélome multiple en rechute ou réfractaire, ayant déjà reçu au moins 2 lignes thérapeutiques dont le lénalidomide et le bortézomib, et dont la maladie a progressé au cours de leur dernière ligne de traitement.
Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of “novel agents”: proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority – if not all – of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.
Background
An overproduction of proinflammatory mediators in severe acute pancreatitis contributes to the systemic inflammatory response, which may lead to multiorgan damage and even death. Thus, ...inflammatory cytokines, e.g., tumor necrosis factor (TNF)-α and interleukin (IL)-1β, may be novel targets for the treatment of acute pancreatitis. The aim of this study was to investigate the therapeutic effects of pomalidomide (or CC-4047), a thalidomide analog and immunomodulatory agent, in acute pancreatitis.
Methods
Acute pancreatitis was induced in C57BL/6 mice by intraperitoneal administration of cerulein (100 μg/kg/h × 8). Pomalidomide was administered (0.5 mg/kg orally) 1 h before the first or 1 h after the last cerulein administration. The severity of the acute pancreatitis was evaluated biochemically and morphologically.
Results
Pretreatment with pomalidomide significantly reduced the plasma levels of amylase and lipase; the histological injury; and the expression of TNF-α, IL-1β, monocyte chemotactic protein-1 (MCP-1), and inducible nitric oxide synthase (iNOS) in cerulein-induced acute pancreatitis. Post-treatment with pomalidomide also decreased the cerulein-induced elevation of plasma amylase and lipase and decreased the pancreatic damage.
Conclusions
Treatment with pomalidomide ameliorated the severity of cerulein-induced acute pancreatitis in mice. Our data suggest that pomalidomide may become a new therapeutic agent in future clinical trials for the treatment of acute pancreatitis.
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