Abstract and Introduction
Abstract
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disorder defined by bone marrow infiltration by lymphoplasmacytic cells as defined by the current classification systems. According to its transition situation between mutated chronic lymphocytic leukemia and multiple myeloma, several new therapeutic alternatives have been proposed for this entity based on the experience with these two well-known conditions together with the highly singular data provided by preclinical models. Thus, in WM two main therapeutic attitudes are possible: the use of conventional therapies based on the administration of single drugs or combinations with alkylating agents, purine analogues and anti-CD20 monoclonal antibodies; or the use of very new combinations that, without rejecting the previously mentioned drugs, include new agents, such as proteasome inhibitors, immunomodulatory agents or even histone deacetylase inhibitors and PI3K/AKT inhibitors, among others. Here we review the most recent results reported for the use of new combinations and new drugs in patients with WM at different stages of the disease.
Introduction
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disorder defined by bone marrow infiltration by lymphoplasmacytic cells as defined by the Revised European American Lymphoma and WHO classification systems, along with the presence of IgM monoclonal gammopathy. From the biological point of view, this condition is very interesting because it is considered a transition from the mature lymphoid B cell after antigenic stimulation in peripheral lymph nodes to the final antibody-secreting plasma cell. In other words, WM is an intermediate disease between mutated chronic lymphocytic leukemia and multiple myeloma (MM), and it shares several characteristics with both entities. Despite this, WM is considerably less frequent than B-cell chronic lymphocytic leukemia (B-CLL) or MM, with an estimated incidence rate of between 3.6 and 5.5 cases per million person-years at risk in the EU and USA. This is the reason for the lack of extensive trials to test the efficacy of traditional and novel therapies. Both characteristics of WM (its intermediate nosologic situation and the lack of therapeutic alternatives) have prompted the use of strategies derived from B-CLL and MM, although the responses have not been as predictable as might have been expected according to previous experience with these two entities.
In this article, we review the most recent results obtained with the use of new drugs and their therapeutic associations in patients with WM at different stages of the disease. Such combinations must be taken with caution, especially if it is considered that the low frequency of WM has not allowed direct comparisons to be made with other more conventional treatment alternatives or between the different novel modalities themselves.