title: Waldenström's macroglobulinemia: a clinical perspective in the era of novel therapeutics.
abstract: Waldenström's macroglobulinemia (WM) is a rare, low-grade malignancy with no established standard of care. Rituximab regimens are most commonly used, supported by their efficacy in hematologic malignancies, including WM. A growing number of investigational regimens for WM have been evaluated in phase II clinical trials, including single-agent and combination strategies that include newer-generation monoclonal antibodies (ofatumumab and alemtuzumab), proteasome inhibitors (bortezomib and carfilzomib), immunomodulatory agents (thalidomide and lenalidomide), phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin pathway inhibitors (everolimus and perifosene), a Bruton's tyrosine kinase inhibitor (ibrutinib), and a histone deacetylase inhibitor (panobinostat). Other novel agents are in early-stage development for WM. International treatment guidelines for WM suggest suitable regimens in the newly diagnosed and relapsed/refractory settings, in accordance with patient age, disease presentation, and efficacy and safety profiles of particular drugs. These factors must be considered when choosing appropriate therapy for individual patients with WM, to maximize response and prolong survival, while minimizing the risk of adverse events. This review article provides a clinical perspective of the modern management of patients with WM, in the context of available trial data for novel regimens and recently updated treatment guidelines.
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece mdimop@med.uoa.gr.
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Medical Oncology, Dana Farber Cancer Center, Boston, MA, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D047428:Protein Kinase Inhibitors
keywords: Waldenström's macroglobulinemia; efficacy; novel agents; safety; treatment guidelines