Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus

Abstract

Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.

BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years

“…[6][7][8] Thus, it is recommended that primary treatment should consist of rituximab-based combinations, to increase response rates and shorten time to response. 5 Nevertheless, rituximab-based combinations are associated with time to first response of 2 to 3 months. Bortezomib affects NF-kB signaling in WM cells 9 and enhances the cytotoxic activity of rituximab in antibody-dependent cellular cytotoxicity assays.…”

“…1,2 Median survival is ;8 to 10 years, and the disease varies from one with indolent course to a disease that needs rapid control. [3][4][5] WM cells express CD20 surface antigen; therefore, rituximab has become a key treatment component; however, it is associated with a modest response rate of ;30% and long time to response. [6][7][8] Thus, it is recommended that primary treatment should consist of rituximab-based combinations, to increase response rates and shorten time to response.…”

Survival outcomes of secondary cancers in patients with waldenström macroglobulinemia: An analysis of the SEER database

“…Presence of an indolent hematologic malignancy should not deter clinicians from pursuing age-appropriate cancer screening. This should be emphasized in updated consensus guidelines for the management of patients with WM [18,28]. …”

Lung consolidation as a rare presentation of lymphoplasmacytic lymphoma with extramedullary Waldenström’s macroglobulinemia

“…Treatment options are usually based on multiple factors; these factors include the need for rapid disease control, age, candidacy for autologous transplantation, comorbidities, presence of cytopenias, hyperviscosity, lymphadenopathy, IgM-related end-organ damage, and patients’ preferences [16]. …”