Waldenstrom macroglobulinemia (WM) is a rare and slow-growing type of non-Hodgkin lymphoma that originates in specific white blood cells called B lymphocytes. This condition is characterized by an overproduction of an abnormal protein known as immunoglobulin M (IgM), which can accumulate in the blood and various tissues. Understanding WM and its management options is an important step for individuals navigating this diagnosis.
Determining the Need for Treatment
Not every individual diagnosed with Waldenstrom macroglobulinemia requires immediate treatment upon diagnosis. A common approach for many patients is “watch and wait,” also known as active surveillance, where healthcare providers closely monitor the disease’s progression without initiating therapy. This strategy is appropriate for those who do not exhibit symptoms or signs of disease progression that would necessitate intervention.
Treatment typically begins when the disease starts causing significant symptoms or complications. Treatment is initiated for indicators such as symptomatic hyperviscosity syndrome, causing issues like headaches, vision changes, or bleeding. Other triggers include significant anemia, causing fatigue and weakness, or a notable decrease in platelet counts, or thrombocytopenia, increasing bleeding risk. Neuropathy, characterized by numbness or tingling, and constitutional “B symptoms” such as unexplained fevers, drenching night sweats, or unintentional weight loss, also signal a need for treatment.
Targeted Therapies and Monoclonal Antibodies
Modern treatments for Waldenstrom macroglobulinemia often involve targeted therapies and monoclonal antibodies, which focus on specific pathways or markers on cancer cells. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors block a protein crucial for WM cell growth and survival. Ibrutinib and zanubrutinib are examples of BTK inhibitors commonly used in this setting.
Monoclonal antibodies are proteins that recognize and attach to specific markers on the surface of cancerous lymphocytes. Rituximab, for instance, targets the CD20 protein found on B-lymphocytes, including the malignant cells in WM. This helps the immune system identify and destroy cancer cells. These agents can be used as initial therapy, either alone or in combination with other drugs. Their side effects differ from traditional chemotherapy, potentially including diarrhea, fatigue, or muscle aches with BTK inhibitors, or infusion-related reactions with rituximab.
Chemotherapy and Chemoimmunotherapy
Chemotherapy agents work by attacking rapidly dividing cells, a characteristic of cancer cells, though healthy cells can also be affected. In Waldenstrom macroglobulinemia, commonly used chemotherapy drugs include bendamustine and cyclophosphamide. These medications interfere with cancer cell growth and multiplication, leading to their destruction.
Chemoimmunotherapy combines traditional chemotherapy with a monoclonal antibody to enhance effectiveness. A widely used chemoimmunotherapy regimen for WM is the combination of bendamustine and rituximab, known as BR. This combination combines chemotherapy’s cell-killing power with rituximab’s targeted immune response. While effective, these regimens can cause more systemic side effects, such as myelosuppression (low blood counts), nausea, or fatigue, compared to some targeted agents.
Supportive Care for Symptom Management
Supportive care measures manage the complications of Waldenstrom macroglobulinemia and improve patient comfort and well-being. Plasmapheresis is a specialized blood-filtering procedure that rapidly removes excess IgM protein from the blood. It alleviates hyperviscosity syndrome symptoms like headaches, vision disturbances, or neurological changes by reducing blood thickness.
While plasmapheresis offers immediate relief, it is a temporary measure to stabilize patients while long-term treatments reduce IgM production. Other supportive measures include blood transfusions for individuals experiencing severe anemia, improving fatigue and weakness. Intravenous immunoglobulin (IVIG) may be administered to patients who develop low levels of normal antibodies, reducing recurrent infections.
Advanced and Salvage Therapies
For patients whose Waldenstrom macroglobulinemia has relapsed or is resistant to standard therapies, advanced and salvage options are considered. Autologous stem cell transplantation is an intensive procedure that involves collecting a patient’s healthy blood stem cells, followed by high-dose chemotherapy to eliminate cancer cells, and then reinfusing the cells to restore bone marrow function. This option is generally reserved for younger, healthier patients who can tolerate the treatment.
Clinical trials offer access to new treatments not yet widely available. These studies investigate novel drugs, combinations, or approaches, offering potential benefits for individuals with refractory or relapsed disease. Patients are encouraged to discuss eligibility for clinical trials with their healthcare team to explore these possibilities.