title: Update on therapeutic options in Waldenström macroglobulinemia.
abstract: Waldenström macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells (LPCs), along with demonstration of an IgM monoclonal gammopathy in the blood. WM remains incurable, with 5-6 yr median overall survival for patients with symptomatic WM. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either in monotherapy or in combination. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival are short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to develop new targeted therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors, of them bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Many agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM.
authors.affiliation: Kirsch Laboratory for Waldenström macroglobulinemia, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI) and Harvard Medical School, Boston, MA, USA. x-leleu@chru-lille.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Julie
authors.initials: J
authors.lastname: Gay
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Moreau
authors.forename: Stephanie
authors.initials: S
authors.lastname: Poulain
authors.forename: Remy
authors.initials: R
authors.lastname: Dulery
authors.forename: Berenice Bro Des
authors.initials: BB
authors.lastname: Champs
authors.forename: Daniela
authors.initials: D
authors.lastname: Robu
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003937:Diagnosis, Differential; D006801:Humans; D007167:Immunotherapy; D015398:Signal Transduction / Q000187:drug effects; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents