title: Current treatment options and investigational drugs for Waldenstrom's Macroglobulinemia.
abstract: Waldenström's Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data. Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM. Recently, the Bruton's tyrosine kinase inhibitor ibrutinib has been licensed for use in WM with exciting results. Several investigational single agent and combination regimens are being evaluated for response, efficacy and tolerability in phase II clinical trials, including new generation monoclonal antibodies (ofatumumab), immunomodulatory agents (thalidomide and lenalidomide), proteasome inhibitors (bortezomib and carfilzomib), Bruton's tyrosine kinase inhibitors (ibrutinib and acalabrutinib), phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin pathway inhibitors (everolimus and perifosene), and histone deacetylase inhibitors (panobinostat) both in the setting of newly diagnosed and relapsed/refractory disease. Expert opinion: WM therapeutic approach should be individualized for each patient in accordance to the intensity of the disease characteristics, age, comorbidities, efficacy, tolerability and safety profile of each drug.
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital , Athens , Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital , Athens , Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital , Athens , Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: a Department of Clinical Therapeutics , National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital , Athens , Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D015507:Drugs, Investigational
keywords: Waldenström’s Macroglobulinemia; ibrutinib; investigational agents; rituximab; therapy