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

From the Guidelines

Waldenström macroglobulinemia (WM) is a rare, incurable, low-grade lymphoplasmacytic lymphoma characterized by the presence of immunoglobulin-M (IgM)-secreting clonal cells in the bone marrow, with a somatic activating mutation in the MYD88 gene found in >90% of patients 1.

Key Characteristics

• The disease is often associated with hyperviscosity syndrome, cytopenias, hemolytic anemia, peripheral neuropathy, hepatomegaly, splenomegaly, and organomegaly 1.
• Patients may present with symptoms such as recurrent fevers, night sweats, fatigue, and weight loss 1.
• The presence of IgM monoclonal protein in the blood is a hallmark of the condition, and diagnosis requires bone marrow biopsy showing lymphoplasmacytic lymphoma cells 1.

Treatment Approach

• Treatment options include chemotherapy, immunotherapy, targeted therapies, and plasmapheresis to reduce blood viscosity 1.
• The Mayo Clinic Cancer Center recommends a risk-adapted approach to treatment, with bendamustine-rituximab as primary therapy for bulky disease, profound hematologic compromise, or constitutional symptoms attributable to WM 1.
• Ibrutinib is efficacious in patients with relapsed or refractory disease harboring MYD88 L265P mutation, and autologous stem cell transplantation may be considered in select patients with chemosensitive disease 1.

Management Considerations

• Not all patients require immediate treatment, and some with asymptomatic disease can be monitored with a "watch and wait" approach 1.
• Routine rituximab maintenance should be avoided, and plasma exchange should be promptly initiated before cytoreduction for hyperviscosity-related symptoms 1.
• Participation in clinical trials is recommended, if available, at every stage of WM, to improve treatment outcomes and quality of life 1.

From the FDA Drug Label

The safety and efficacy of IMBRUVICA in patients with WM were demonstrated in two single-arm trials and one randomized, controlled trial. Study 1118 (NCT01614821), an open-label, multi-center, single-arm trial was conducted in 63 previously treated patients with WM The responses were assessed by investigators and an IRC using criteria adopted from the International Workshop of Waldenström’s Macroglobulinemia.

• Waldenström’s Macroglobulinemia is characterized by:
  • Elevated serum IgM levels
  • Presence of lymphoplasmacytic cells in the bone marrow
  • Symptoms such as anemia, fatigue, and weight loss
  • Response to treatment with IMBRUVICA, as measured by partial response or better, per IRC assessment 2 2

From the Research

Characterization of Waldenström Macroglobulinemia

• Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein 3, 4, 5, 6.
• Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity 3, 4, 5, 6.
• The presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis 3, 4, 5, 6.
• The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients 3, 4, 5, 6.

Predictive Characteristics

• Age, albumin, hemoglobin level, platelet count, β2 microglobulin, Lactate dehydrogenase (LDH), and monoclonal IgM concentrations are characteristics that are predictive of outcomes 3, 4, 5.
• These characteristics help in risk stratification and management of the disease 3, 4, 5.

Disease-Related Complications

• Direct invasion of malignant cells into tissues like lymph nodes and spleen, along with the immune response related to IgM, can lead to various health complications, such as cytopenias, hyperviscosity, peripheral neuropathy, amyloidosis, and Bing-Neel syndrome 5, 7.
• Monoclonal IgM circulation and deposition can also result in a variety of disease-related complications 7.

Treatment and Management

• Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop 3, 4, 5, 6.
• Chemoimmunotherapy has historically been considered the preferred treatment for WM, wherein the combination of rituximab and nucleoside analogs, alkylating drugs, or proteasome inhibitors has exhibited notable efficacy in inhibiting tumor growth 5, 6.
• Recent studies have provided evidence that Bruton Tyrosine Kinase inhibitors (BTKI), either used independently or in conjunction with other drugs, have been shown to be effective and safe in the treatment of WM 5, 7.