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.

Utility of mTOR Inhibition in Hematologic Malignancies

“…WM is a rare, low-grade lymphoplasmacytic B-cell lymphoma accompanied by serum IgM monoclonal gammopathy [61]. mTOR inhibitors have been investigated in WM based on results of in vitro studies demonstrating activation of PI3K/Akt/mTOR signaling in WM cells.…”

Past, Present, and Future of Rituximab—The World’s First Oncology Monoclonal Antibody Therapy

“…Lymphoplasmacytic lymphoma follows an indolent clinical path and is incurable but rare. Due to its indolent nature, it has a median survival of 5–10 years in symptomatic patients ( 58 , 59 ). The disease comprises cells most similar to those intermediate between small lymphocytes and true plasma cells, with features of both, including secretion of an IgM paraprotein ( 17 ).…”

Immunomodulator alemtuzumab therapy in kidney transplantation

“…(3) Second-line therapy for relapsed or refractory angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, or anaplastic large cell lymphoma in non-candidates for high-dose therapy with autologous stem cell rescue. (4) Single agent salvage therapy for Waldenstrom's macroglobulinemia or lymphoplasmacytic lymphoma that does not respond to primary therapy or for progressive or relapsed disease [54] . Alemtuzumab continues to be considered an investigational and experimental drug for conditions such as multiple sclerosis [55] , anti-neutrophil cytoplasmic antibody-associated vasculitides [56] , graft versus host disease [57] , sporadic inclusion-body myositis [58] , aplastic anemia, pure red cell and pure white cell aplasia [59] , refractory acute rejection (RAR) and bronchiolitis obliterans syndrome (BOS) [60] .…”