Updates on Waldenström macroglobulinemia treatment formed by an international consensus panel were recently finalized and published in The Lancet Haematology.
Criteria for the treatment of Waldenström macroglobulinemia (WM) were recently updated by an international consensus panel, following the panel's formation and initial discussion at the 10th annual International Workshops for Waldenström Macroglobulinemia (IWWM) in 2018. After 2 subsequent teleconferences in June 2019 and January 2020, the updates were finalized and published in The Lancet Haematology.
WM is a rare form of non-Hodgkin lymphoma, and treatment options have evolved in recent years. Members of the consensus panel were chosen based on their expertise in the rare disease and their participation in discussions at the 10th annual IWWM conference. The review includes recommendations for treatment and clinical trial enrollment, as well as potential priorities for future clinical trials.
Where current treatment options are concerned, the authors highlighted anti-CD20 monoclonal antibody monotherapy, chemoimmunotherapy, proteasome inhibitors in combination with rituximab, BTK inhibitors, maintenance rituximab, and hematopoietic stem-cell transplantation as potential options.
In the first-line setting, the consensus update was that chemoimmunotherapy (cyclophosphamide, dexamethasone, and rituximab [CDR] or bendamustine plus rituximab); the proteasome inhibitor bortezomib, dexamethasone, and rituximab (BDR); the BTK inhibitor ibrutinib alone; and ibrutinib plus rituximab are the preferred options for symptomatic WM. The panel also noted that there is not sufficient data to recommend ibrutinib plus rituximab over ibrutinib monotherapy.
The suggested first-line treatments are also appropriate in relapsed or refractory WM, the panel agreed, but it did not come to a consensus on which therapy or combination had the best safety and efficacy, largely due to a lack of prospective randomized studies comparing them.
With ibrutinib specifically, the panel recommended PCR-based assays to test for MYD88 and L265P mutations, and it recommended against ibrutinib monotherapy in patients without MYD88 mutations. Gene sequencing should follow a negative PCR test, they wrote, before making treatment decisions based on the PCR assay.
Novel proteasome inhibitors in addition to bortezomib are also available and recommended by the National Comprehensive Cancer Network (NCCN) in the United States, including carfilzomib and ixazomib—both in combination with rituximab and dexamethasone, the panel noted.
The authors make it clear that treatment should be based on individual patient needs, drug availability, and coverage depending on guidelines, but the overall algorithm presented in the guidelines is as follows:
Preferred treatment options
Other treatment options
The panel also recommends that symptomatic patients with WM enroll in relevant ongoing clinical trials. Even with more targeted therapies for WM being developed, their use still requires optimization, according to the panel. As for future clinical trial priorities, large international collaborations between academia, industry, regulatory authorities, and the global patient community are necessary due to the rarity of WM.
“The goal of future studies should be the development of personalized treatment approaches,” the panel wrote. “Another important aspect for clinical trials in Waldenström macroglobulinemia treatment is the determination of clinically relevant end points. Overall survival and progression-free survival might not be feasible primary end points, and validated surrogate endpoints should be developed to allow timely evaluation of new treatments.”
They added that despite low rates of complete response with current therapy options, new options could lead to a higher proportion of complete response in patients with WM, and then implementing minimal residual disease-based approaches could help guide treatment duration.
Efficacy versus toxicity and financial burden are also issues in WM treatment, as in other cancers, that need to be explored as clinical trials continue. Looking to the future of WM treatment, the panel concluded, “Cost-effectiveness, toxicity, and quality of life are major concerns and the sustainability of the health-care system with the increasing use of expensive therapies should remain a focus when designing future clinical trials.”
1. Castillo JJ, Advani RH, Branagan AR, et al. Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol. 2020;7(11): e827–e837. doi: 10.1016/S2352-3026(20)30224-6