What is Waldenström's macroglobulinemia (Waldenström's macroglobulinemia)?

From the Guidelines

Waldenstrom macroglobulinemia is a rare, incurable cancer characterized by an overproduction of immunoglobulin M (IgM) protein, which can cause blood thickening and circulation problems, primarily affecting older adults and more common in men than women. This condition is a type of lymphoplasmacytic lymphoma that begins in the white blood cells called B lymphocytes 1. The disease progresses slowly, and symptoms include fatigue, unexplained weight loss, bleeding from the nose or gums, visual problems, and neurological symptoms like headaches, dizziness, or confusion.

Key Characteristics and Treatment Options

• The disease is not curable but can be managed effectively for many years with treatment options including chemotherapy drugs like rituximab, ibrutinib, or bendamustine; targeted therapy; plasmapheresis to remove excess proteins from the blood; and stem cell transplantation in certain cases 1.
• Regular monitoring of blood counts and protein levels is essential for patients with this condition, as complications can include hyperviscosity syndrome, neuropathy, and an increased risk of other cancers 1.
• Treatment recommendations should be based on individual patient considerations, including 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 1.

Recent Guidelines and Recommendations

• The Mayo Clinic Cancer Center Myeloma, Amyloidosis and Dysproteinemia and Lymphoma Disease-Oriented Groups recommend bendamustine-rituximab as primary therapy for bulky disease, profound hematologic compromise, or constitutional symptoms attributable to WM, and dexamethasone-rituximab-cyclophosphamide as an alternative, particularly for nonbulky WM 1.
• Ibrutinib is efficacious in patients with relapsed or refractory disease harboring MYD88 L265P mutation, and a bortezomib-rituximab–based option is reasonable for relapsed or refractory disease in the absence of neuropathy 1.

From the Research

Definition and Characteristics of Waldenstrom Macroglobulinemia

• Waldenstrom macroglobulinemia (WM) is a B-cell lymphoplasmacytic lymphoma characterized by monoclonal immunoglobulin M protein in the serum and infiltration of bone marrow with lymphoplasmacytic cells 2.
• It is a rare B-cell disorder primarily characterized by bone marrow infiltration with lymphoplasmacytic cells, along with demonstration of an IgM monoclonal gammopathy 3.
• WM is characterized by the uncontrolled accumulation of malignant lymphoplasmacytic cells, mainly in the bone marrow, and monoclonal IgM production 4.

Clinical Features and Diagnosis

• Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity 5.
• The presence of IgM monoclonal protein associated with ≥ 10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis 5.
• The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients, but MYD88 is not required for the diagnosis 5.

Treatment and Management

• Asymptomatic patients can be observed without therapy, while symptomatic patients require treatment 2, 3.
• First-line therapy should consist of the monoclonal anti-CD20 antibody, rituximab, given typically in combination with other agents 2.
• Recommended first-line therapy can be chemoimmunotherapy or a covalent Bruton tyrosine kinase inhibitor 5.
• Active agents in the management of WM can be broadly classified as rituximab-alkylator combination therapy, proteasome inhibitor-based therapy, and Bruton's tyrosine kinase inhibitor-based therapy 6.

Prognosis and Relapse

• Despite advances in therapy, WM remains incurable, with 5-6 years median overall survival of patients in symptomatic WM 3.
• Relapse is almost inevitable in WM but may occur years after initial therapy 2.
• Age, albumin, hemoglobin level, platelet count, β2 microglobulin, Lactate dehydrogenase (LDH), and monoclonal IgM concentrations are characteristics that are predictive of outcomes 5.