title: Novel agents for multiple myeloma to overcome resistance in phase III clinical trials.
abstract: The incorporation of novel agents such as bortezomib and lenalidomide into initial therapy for multiple myeloma has improved the response rate of induction regimens. Also, these drugs are being increasingly used in the peri-transplant setting for transplant-eligible patients, and as part of consolidation and/or maintenance after front-line treatment, including in transplant-ineligible patients. Together, these and other strategies have contributed to a prolongation of progression-free survival (PFS) and overall survival (OS) in myeloma patients, and an increasing proportion are able to sustain a remission for many years. Despite these improvements, however, the vast majority of patients continue to suffer relapses, which suggests a prominent role for either primary, innate drug resistance, or secondary, acquired drug resistance. As a result, there remains a strong need to develop new proteasome inhibitors and immunomodulatory agents, as well as new drug classes, which would be effective in the relapsed and/or refractory setting, and overcome drug resistance. This review will focus on novel drugs that have reached phase III trials, including carfilzomib and pomalidomide, which have recently garnered regulatory approvals. In addition, agents that are in phase II or III, potentially registration-enabling trials will be described as well, to provide an overview of the possible landscape in the relapsed and/or refractory arena over the next 5 years.
authors.affiliation: Department of Lymphoma/Myeloma, and Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: rorlowsk@mdanderson.org.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use; D000077767:Panobinostat; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000627:therapeutic use; D010880:Piperidines; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D011725:Pyridines; D012074:Remission Induction; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007155:Immunologic Factors; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D061988:Proteasome Inhibitors; D011725:Pyridines; D013844:Thiazoles; D010767:Phosphorylcholine; C546027:elotuzumab; C105905:perifosine; D013792:Thalidomide; D000077337:Vorinostat; C524865:carfilzomib; D000077767:Panobinostat; C467566:pomalidomide; C526575:masitinib