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How to Sequence Therapies in Waldenström Macroglobulinemia

  • Lymphoma (JL Muñoz, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

There are multiple treatment options in patients with Waldenström macroglobulinemia, including chemotherapy, monoclonal antibodies, proteasome inhibitors, and covalent Bruton tyrosine kinase (BTK) inhibitors. The choice of therapy should take into account the patient’s clinical presentation, comorbidities, and preferences. A thorough discussion should take place to outline the administration, safety, and efficacy of the regimens under consideration. The patient’s genomic profile can provide insightful information for the treatment selection. In the frontline and relapsed settings, we favor ibrutinib monotherapy over chemoimmunotherapy or proteasome inhibitor-based regimens in patients with MYD88 and without CXCR4 mutations. For patients with MYD88 and CXCR4 mutations or without MYD88 or CXCR4 mutations, chemoimmunotherapy or proteasome inhibitor-based regimens are favored, but efficacy data with ibrutinib in combination with rituximab and with novel covalent BTK inhibitors are emerging. Autologous stem cell transplant should be considered in special cases in the relapsed setting. Participation in clinical trials is positively encouraged in WM patients in frontline and relapsed settings. Agents of interest include the BCL2 antagonist venetoclax, the CXCR4 inhibitor mavorixafor, and the non-covalent BTK inhibitors pirtobrutinib and ARQ-531.

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Authors and Affiliations

  1. Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Mayer 221, Boston, MA, 02215, USA

    Shayna Sarosiek MD, Steven P. Treon MD, PhD & Jorge J. Castillo MD

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  1. Shayna Sarosiek MD
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  2. Steven P. Treon MD, PhD
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  3. Jorge J. Castillo MD
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Correspondence to Jorge J. Castillo MD.

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Shayna Sarosiek declares that she has no conflict of interest. Steven P. Treon has received research funding from AbbVie/Pharmacyclics, Janssen, BeiGene, and Eli Lilly; and has received compensation for service as a consultant from AbbVie/Pharmacyclics, Janssen, BeiGene, and Bristol-Myers Squibb. Jorge J. Castillo has received research funding from AbbVie, BeiGene, Janssen, Pharmacyclics, and TG Therapeutics; and has received compensation for service as a consultant from AbbVie, BeiGene, Janssen, Pharmacyclics, and Roche.

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Sarosiek, S., Treon, S.P. & Castillo, J.J. How to Sequence Therapies in Waldenström Macroglobulinemia. Curr. Treat. Options in Oncol. 22, 92 (2021). https://doi.org/10.1007/s11864-021-00890-9

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