Article

Multiple myeloma.

Myeloma Unit, Division of Hematology, University of Turin, AOU S. Giovanni Battista, Turin, Italy.
New England Journal of Medicine (Impact Factor: 54.42). 03/2011; 364(11):1046-60. DOI: 10.1056/NEJMra1011442
Source: PubMed
0 Followers
 · 
99 Views
  • Source
    Blood Cancer Journal 01/2015; 5:e285. DOI:10.1038/bcj.2015.7 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Multiple myeloma (MM) is a plasma cell disorder characterized by bone marrow suppression, skeletal complications, renal dysfunction and often a long course involving multiple different treatments. Over the past decade, novel treatment modalities have resulted in significant improvements in progression-free and overall survival. Histone deacetylase inhibitor(s) (HDACi) appear to offer an alternative therapeutic avenue in the treatment for MM likely through their impact on HDAC-6 function, and possibly through epigenetic effects as well. Panobinostat, a novel pan-HDAC (Pan-Dac) inhibitor, is of particular interest due to its broad HDAC inhibition, selectivity toward malignant cells and oral bioavailability.Areas covered: In this review, the authors discuss the potential therapeutic benefits of panobinostat, in the treatment of MM. Topics covered include pleiotropic effects of HDAC modulation in MM, pharmacokinetics and pharmacodynamics of panobinostat, as well as available data demonstrating clinical efficacy and safety from clinical trials.Expert opinion: Panobinostat is a novel Pan-Dac inhibitor with a number of different mechanisms of action related to its impact on myeloma. Data in combination with bortezomib suggests significant improvement in progression-free survival when compared with control treatment, as well as the ability to overcome bortezomib resistance. These factors suggest that the addition of panobinostat to our current treatment paradigm will offer new and important treatment options for our patients in all phases of myeloma treatment.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple myeloma (MM) is a unique cancer paradigm for investigating the mechanisms involved in the transition from a premalignant condition (monoclonal gammopathy of undetermined significance) into a malignant disease (MM). In the pathogenesis of myeloma, the dialogue between plasma cells and their microenvironment is as important as the genotypic characteristics of the tumor clone. MM is genetically highly complex, with almost all patients displaying cytogenetic abnormalities and frequent intraclonal heterogeneity that play a critical role in the outcome of the disease. In fact, it is likely that myeloma will soon no longer be considered as a single entity. This, along with the availability of an unexpected number of new treatment possibilities, has reinforced the need for better tools for prognosis and for monitoring treatment efficacy through minimal residual disease techniques. The outcome of MM patients has significantly improved in the last 2 decades, first through the introduction of high-dose therapy followed by autologous stem cell transplantation and, more recently, due to the use of proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide). Moreover, the need to reexamine the diagnostic criteria of early MM and the possibility of early intervention opens up new therapeutic avenues. New drugs are also emerging, including second- and third-generation proteasome inhibitors and immunomodulators, monoclonal antibodies, histone deacetylase inhibitors, and kinesin spindle protein inhibitors, among others. Our goal is to find a balance among efficacy, toxicity, and cost, with the ultimate aim of achieving a cure for this disease. © 2014 by The American Society of Hematology. All rights reserved.