Over the next month, the Lymphoma Hub will be focusing on a new educational theme: Advances in treating Waldenström's macroglobulinemia. This article introduces the topic and summarizes some of the latest advances and key clinical trials in the field.
Waldenström's macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma that usually affects older patients (> 65 years). It is characterized by the accumulation of malignant immunoglobulin M (IgM)-secreting lymphoplasmacytic cells in the bone marrow and other organs.1 Although patients are often diagnosed at the asymptomatic, or ‘smoldering’ stage, they are typically not treated until the disease progresses, as curative therapy is not available and current standard treatment regimens are not proven to prolong the survival of patients at these early stages. Most patients will become symptomatic during the progression of the disease, due to anemia, hyperviscosity syndrome, neuropathy, extramedullary disease, or other processes, thereby requiring therapy.1
Over 90% of patients with WM have the point mutation L265P in MYD88, while those without this mutation tend to have higher risk of aggressive transformation to diffuse large B-cell lymphoma, and a worse survival outcome.1 Approximately, 30–40% of patients with WM also have recurrent CXCR4 mutations, which are associated with higher IgM levels, higher risk of developing symptomatic hyperviscosity, but lower rates of extramedullary disease, such as lymphadenopathy and hepatosplenomegaly.1
Current treatment options and outcomes
The current treatment options for patients with symptomatic WM include anti-CD20 monoclonal antibodies, alkylating agents, proteasome inhibitors, and Bruton tyrosine kinase (BTK) inhibitors.
Anti-CD20 monoclonal antibodies
Rituximab, alone or in combination with other agents, is the most common treatment for WM. As a single agent, it was shown to have an overall response rate (ORR) of 40–50%, with a median progression-free survival (PFS) of 12–24 months. However, rituximab usage has been associated with paradoxical IgM flares and intolerance.1
Last year, at the 24th European Hematology Association (EHA) Annual Congress, the Lymphoma Hub talked to Simon Rule about the MabCute phase III study (NCT01461928). This compared the use of subcutaneous (SC) versus intravenous (IV) rituximab, and extended maintenance with SC rituximab versus observation, in patients with indolent non-Hodgkin lymphoma, including WM. He reported that there was no additional toxicity associated with SC rituximab compared to IV, even in the extended maintenance cohort. Watch the video below for more on the PFS results.