Treatment of WM
At present, the only drug approved by the European Medicines Agency (EMA) and the FDA for WM is ibrutinib. Despite being the most active single agent therapy for WM, incomplete responses are common. Furthermore, other safety concerns, as well as several associated drug interactions, may limit the use of ibrutinib.
Nondrug therapies include plasmapheresis, which is rapid-acting but often transient, warranting additional systemic therapy. With respect to systemic therapies, extended rituximab combination regimens are most frequently used. For example, rituximab, cyclophosphamide, and dexamethasone (DRC) for 6 cycles has demonstrated good safety, but efficacy data have been variable, with incomplete responses seen in the long term. Bendamustine plus rituximab (BR) for 4 to 6 cycles has shown activity with durable responses; however, infectious complications and hematologic toxicities could limit use in older patients.1
Various novel agents are currently under investigation, including both bortezomib and ixazomib. In phase 2 studies, bortezomib has demonstrated activity (alone or in combination with rituximab) in both newly diagnosed and relapsed settings. Potential benefits include the lack of a transient rise in serum IgM levels seen with other rituximab-based combination therapies. Preliminary efficacy data with ixazomib (in combination with dexamethasone and rituximab) have been positive, but the findings are still immature. Other investigational agents include thalidomide, lenalidomide, and everolimus.1
Given the presently available treatment options, the main goals of therapy are to reduce tumor load and control symptoms. Other relevant considerations include the level of tumor bulk, predominant symptomatology, and risk or presence of hyperviscosity. In contrast, some patients may not require prompt initiation of therapy, such as those with mild symptoms; these patients should instead be monitored carefully. The administration of intravenous immunoglobulin is only recommended with the recurrence of severe infections, while vaccinations are recommended for all patients.
Fostering Collaboration in Clinical Trials
With newer therapies on the horizon, improving collaboration in clinical trials remains an optimal strategy for advancing the development of novel agents. The creation of research infrastructures is one strategy to increase the global effects of funded research, especially for rare diseases. One example is the formation of shared databases and registries that may enhance understanding of disease pathogenesis, resulting in more innovative treatment options. Furthermore, international collaboration among experts allows for shared expertise and could lead to the initiation of multicenter clinical trials.2
Effective collaboration involves several key stakeholders, including patients, funding bodies, researchers, regulatory agencies, patient advocacy groups, and drug companies. Ultimately, closing the gap between research and clinical care will require teamwork and cooperation between these groups.2
1. Dimopoulos MA, Kastritis E. How I treat Waldenström macroglobulinemia. Blood. 2019;134:2022-2035.
2. Julkowska D, Austin CP, Cutillo CM, et al. The importance of international collaboration for rare diseases research: a European perspective. Gene Ther. 2017;24:562-571.