Elsevier

The Lancet Haematology

Volume 7, Issue 11, November 2020, Pages e827-e837
The Lancet Haematology

Review
Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia

https://doi.org/10.1016/S2352-3026(20)30224-6Get rights and content

Summary

Waldenström macroglobulinaemia is an indolent B-cell lymphoma with clearly defined criteria for diagnosis, initiation of therapy, and response, which was established by consensus panels at previous International Workshops for Waldenström Macroglobulinaemia (IWWM). The treatment options for Waldenström macroglobulinaemia continued to be researched after the publication of the eighth IWWM consensus recommendations in 2016, and at the tenth IWWM in New York, USA (October, 2018) an international consensus panel was formed to update treatment recommendations. Participants were selected as members of the consensus panel based on their expertise on Waldenström macroglobulinaemia. The initial live discussion took place during the tenth IWWM meeting and two separate teleconferences were held in June, 2019, and January, 2020, to refine recommendations. No external or financial support was received for the elaboration of these recommendations. According to these updated consensus recommendations, alkylating drugs (bendamustine, cyclophosphamide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well as BTK inhibitors (ibrutinib), alone or in combination with rituximab, are preferred first-line therapy options for symptomatic patients with Waldenström macroglobulinaemia. In previously treated patients with Waldenström macroglobulinaemia who had an initial durable response, reuse of a previous regimen or another primary therapy regimen are acceptable options. Novel BTK inhibitors (acalabrutinib, zanubrutinib, tirabrutinib) and the BCL2 antagonist venetoclax appear safe and active, and represent emerging options for the treatment of Waldenström macroglobulinaemia. The choice of therapy should be guided by the patient's clinical profile, genomic features, and drug availability.

Introduction

Waldenström macroglobulinaemia is characterised by the malignant accumulation of IgM-secreting lymphoplasmacytic lymphoma cells in the bone marrow and other organs.1 Since the initial development of treatment recommendations at the second International Workshop for Waldenström macroglobulinaemia (IWWM-2) in 2002,2 treatment options for patients with Waldenström macroglobulinaemia have evolved, and treatment recommendations have been updated at subsequent workshops.3, 4, 5, 6 As part of the IWWM-10 (New York, NY, USA, Oct 11–13, 2018), a consensus panel was established to update the treatment recommendations for Waldenström macroglobulinaemia on the basis of the latest data from clinical trials.

Participants of the IWWM-10 were selected as members of the consensus panel depending on their expertise on Waldenström macroglobulinaemia and their participation in the discussions. The initial live open discussion took place during the actual IWWM-10 meeting in October, 2018, in New York. Following this meeting, two separate teleconferences (June, 2019, and January, 2020) were undertaken to further discuss and refine recommendations until consensus was reached. All consensus panel members participated in the live meeting and teleconferences. No external or financial support was received for the elaboration of these recommendations.

Section snippets

Anti-CD20 monoclonal antibody monotherapy

The chimeric anti-CD20 monoclonal antibody rituximab is the most commonly used monotherapy for the treatment of Waldenström macroglobulinaemia in the USA.7 Rituximab monotherapy has been prospectively evaluated in several studies (table 1). Rituximab can induce IgM flares, which are rapid increases of serum IgM (≥25%) shortly after rituximab exposure and can occur in 50% of patients with Waldenström macroglobulinaemia who have rituximab monotherapy.12, 13 IgM flares occur more commonly with

Recent clinical trials

The consensus panel endorses enrolment of patients with symptomatic Waldenström macroglobulinaemia in ongoing clinical trials (appendix p 2).

Priorities in future clinical trials

Treatment options for patients with Waldenström macroglobulinaemia are increasing and more targeted therapies are being used in everyday practice and clinical trials. However, the use of currently available targeted therapies needs further optimisation. Waldenström macroglobulinaemia is a rare disease; therefore, it is important to prioritise studies that will drive the development of innovative, effective, and safer therapies. Large studies require international collaboration and partnerships

Search strategy and selection criteria

To formulate recommendations based on evidence, a literature search was done of PubMed with the keyword “Waldenström” between Jan 1, 2010, and Feb 29, 2020, with no language restrictions. Abstract presentations from the annual meetings of the American Society of Hematology, the European Hematology Association, the American Society of Clinical Oncology, the European Society of Medical Oncology, the International Conference in Malignant Lymphoma, and the International Workshop for Waldenström

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