How I treat Waldenström macroglobulinemia

Abstract

Waldenström macroglobulinemia (WM) is a B-cell neoplasm manifested by the accumulation of clonal immunoglobulin (Ig)M-secreting lymphoplasmacytic cells. MYD88 and CXCR4 warts, hypogammaglobulinemia, infections, myelokathexis syndrome-like somatic mutations are present in >90% and 30% to 35% of WM patients, respectively, and impact disease presentation, treatment outcome, and overall survival. Familial predisposition is common in WM. Asymptomatic patients should be observed. Patients with disease-related hemoglobin <10 g/L, platelets <100 × 109/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or transformed disease should be considered for therapy. Plasmapheresis should be used for patients with symptomatic hyperviscosity and before rituximab for those with high serum IgM levels to preempt a symptomatic IgM flare. Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression and secondary malignancies, and planning for future autologous stem cell transplantation. Frontline treatments include rituximab alone or rituximab combined with alkylators (bendamustine and cyclophosphamide), proteasome inhibitors (bortezomib and carfilzomib), nucleoside analogs (fludarabine and cladribine), and ibrutinib. In the salvage setting, an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered. Investigational therapies under development for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 signaling, novel proteasome inhibitors, and chimeric antigen receptor-modified T-cell therapy.

18F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders

“…All patients underwent FDG PET/CT before and after therapy. This imaging procedure was able to detect positive findings in 83 % of the patients, a result in sharp contrast with the data of previous studies carried out with the use of conventional imaging that reported liver, spleen, and lymph node involvement in remarkably lower percentages [79]. At baseline, FDG-avid sites included more frequently lymph nodes, bone marrow, extra-nodal or internal organs such as lung and pleura (that can sometimes mimick multiple metastatic lesions), and spleen.…”

“…Based on large series of patients, including our own cohort of 121 patients [78], it has in fact been shown that the clinical presentation of WM is rather heterogeneous, including lymphadenopathy, hepato-splenomegaly, and polyneuropathy in percentages ranging from 20 to 25 %, signs, and symptoms related to the physical, chemical, and immunologic properties of the IgM monoclonal component, and bone marrow clonal cell expansion of variable extent [79].…”

Management of refractory autoimmune hemolytic anemia via allogeneic stem cell transplantation

“…2,5,6 Plasmapheresis rapidly lowers IgM concentrations for immediate disease control. 1 We report for the first time a case of WM with presumed cold-agglutininmediated AIHA refractory to typical therapy, ultimately requiring hematopoietic stem cell transplantation, specifically for anemia control.…”

“…1 Overproduced IgMs can act as cold agglutinins in WM. Upon exposure to cooler temperatures in the periphery, they cause anemia via binding to the erythrocyte Ii-antigen group and classical complement cascade initiation.…”

“…Upon exposure to cooler temperatures in the periphery, they cause anemia via binding to the erythrocyte Ii-antigen group and classical complement cascade initiation. 2 Treatment of cold-agglutinin-mediated autoimmune hemolytic anemia (AIHA) in WM typically targets the pathogenic B-cell clone [1][2][3][4] or the classical complement cascade. 2,5,6 Plasmapheresis rapidly lowers IgM concentrations for immediate disease control.…”