Update on therapeutic options in Waldenström macroglobulinemia
Open Access
- 11 December 2008
- journal article
- review article
- Published by Wiley in European Journal of Haematology
- Vol. 82 (1), 1-12
- https://doi.org/10.1111/j.1600-0609.2008.01171.x
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.Keywords
This publication has 98 references indexed in Scilit:
- Thalidomide and rituximab in Waldenstrom macroglobulinemiaBlood, 2008
- CD27-CD70 interactions in the pathogenesis of Waldenström macroglobulinemiaBlood, 2008
- Waldenstrom MacroglobulinemiaCancer Letters, 2008
- SDF-1/CXCR4 and VLA-4 interaction regulates homing in Waldenstrom macroglobulinemiaBlood, 2008
- Targeting NF-κB in Waldenstrom macroglobulinemiaBlood, 2008
- Dual targeting of the proteasome regulates survival and homing in Waldenström macroglobulinemiaBlood, 2008
- The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemiaBlood, 2007
- A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myelomaBlood, 2006
- Initial immunoglobulin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemiaCancer, 2004
- Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's MacroglobulinemiaSeminars in Oncology, 2003