title: Novel therapeutics in multiple myeloma.
abstract: Most myeloma patients still experience recurrent relapse and eventually become resistant and/or intolerant of effective agents such as corticosteroids, alkylating agents, immune modulators (lenalidomide and thalidomide) or proteasome inhibitors such as bortezomib.  Once this happens average survivals are less than one year. Progress has been made for such patients, however, with the demonstration of clinical benefit of novel proteasome inhibitors (carfilzomib) and immune modulators (pomalidomide). Pomalidomide when used with dexamethasone has activity  in 30-60% of patients depending on disease stage. Carfilzomib is an irreversible proteasome inhibitor with favorable toxicity profile (minimal neuropathy) and response rates of 17-54% depending on the disease stage treated. Novel targets are also being explored. Histone deacetylase  inhibitors such as vorinostat and panobinostat are in phase II testing although results from a randomized trial combining vorinostat with bortezomib were disappointing. Other small molecules or monoclonal antibodies with novel targets such as kinase inhibitors(AKT, CDK5) and cell surface receptors  (e.g. elotuzumab) are undergoing active investigation.
authors.affiliation: Division of Hematology-Oncology, Mayo Clinic in Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, USA. stewart.keith@mayo.edu
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077337:Vorinostat
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007155:Immunologic Factors; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D013792:Thalidomide; D000077337:Vorinostat; C524865:carfilzomib; C467566:pomalidomide