Novel therapies for relapsed myeloma.
Treatment of myeloma relapse needs to be individualized to reflect the effectiveness and toxicities of prior therapies, with consideration given to pragmatic issues such as the tempo of relapse, age of the patient, access to drugs and patient preference. In general, combination therapies have been associated with higher response rates and improved progression-free survival and may be preferable when a rapid response is required. Nevertheless, in a slower-tempo relapse it is unclear at this juncture whether sequencing of drugs or multi-agent combinations offer superior overall survival results. Fortunately, active novel agents that offer further possibilities for some myeloma patients have become available in clinical trials. In this review we will describe the various classes of novel drugs being tested and the pros and cons of preclinical testing, and will particularly focus on two agents with single-agent activity in myeloma: carfilzomib, a proteasome inhibitor, and pomalidomide, a member of the immunomodulatory class of drugs.
Stewart
A Keith
AK
Hematology and Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA. stewart.keith@mayo.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D015507:Drugs, Investigational / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000601:surgery; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D061988:Proteasome Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D016879:Salvage Therapy; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001897:Boronic Acids; D015507:Drugs, Investigational; D006360:Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D009588:Nitrogen Mustard Compounds; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; C524865:carfilzomib; D000069461:Bendamustine Hydrochloride; C467566:pomalidomide; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt