title: Monoclonal antibodies in the treatment of multiple myeloma.
abstract: Despite recent advances in treatment that have significantly improved overall survival, multiple myeloma (MM) remains incurable. Although rituximab, the first monoclonal antibody (MAb) evaluated in MM treatment, provided only very limited benefit, research is ongoing into a number of other MAbs directed against a variety of MM-related target antigens. Given the inherent immune dysfunction associated with MM, newer strategies that may enhance immune function in conjunction with antibodies may also provide a more fruitful clinical approach. Potential MAb targets in MM include growth factors and their receptors, other signalling molecules, and antigens expressed exclusively or predominantly on MM cells. MAb therapy involves a range of mechanisms, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, interference with receptor-ligand interactions, and MAb conjugation to radioisotopes or toxins. The antigens currently targeted in MM therapy are discussed, along with the development status of the corresponding MAb therapeutics. Elotuzumab, an anti-CS1 MAb, has recently achieved clinically meaningful responses when combined with lenalidomide or bortezomib in patients with relapsed and relapsed/refractory MM. Other MAbs are also showing early promise. More ongoing clinical research is required to identify optimal combination regimens and biomarkers that may help predict response to specific MAb-based combinations.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USADepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USAUniversity of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USACentre Rene Gauducheau, Nantes, France.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Jakubowiak
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents