Report of consensus panel 1 from the 11th International Workshop on Waldenstrom's Macroglobulinemia on management of symptomatic, treatment-naïve patients

Christian Buske*, Jorge  J J. Castillo, Jithma  Prasad P. Abeykoon, Ranjana Advani, Suzanne  O O. Arulogun, Andrew  R R. Branagan, Xinxin Cao, Shirley D'Sa, Jian Hou, Prashant Kapoor, Efstathios Kastritis, Marie  J J. Kersten, Veronique LeBlond, Merav Leiba, Jeffrey  V V. Matous, Jonas Paludo, Lugui Qiu, Constantine  S S. Tam, Alessandra Tedeschi, Sheeba  K K. ThomasIbrahim Tohidi-Esfahani, Marzia Varettoni, Josephine  M M. Vos, Ramon Garcia-Sanz, Jesus San-Miguel, Meletios  A A. Dimopoulos, Steven  P P. Treon, Judith Trotman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Consensus Panel 1 (CP1) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with updating guidelines for the management of symptomatic, treatment-naïve patients with WM. The panel reiterated that watchful waiting remains the gold standard for asymptomatic patients without critically elevated IgM or compromised hematopoietic function. For first-line treatment, chemoimmunotherapy (CIT) regimens such as dexamethasone, cyclophosphamide, rituximab (DRC), or bendamustine, rituximab (Benda-R) continue to play a central role in managing WM, as they are effective, of fixed duration, generally well-tolerated, and affordable. Covalent BTK inhibitors (cBTKi) offer a continuous, generally well-tolerated alternative for the primary treatment of WM patients, particularly those unsuitable for CIT. In a Phase III randomized trial updated at IWWM-11, the second-generation cBTKi, zanubrutinib, was less toxic than ibrutinib and induced deeper remissions, thus categorizing zanubrutinib as a suitable treatment option in WM. While the overall findings of a prospective, randomized trial updated at IWWM-11 did not show superiority of fixed duration rituximab maintenance over observation following attainment of a major response to Benda-R induction, a subset analysis showed benefit in patients >65 years and those with a high IPPSWM score. Whenever possible, the mutational status of MYD88 and CXCR4 should be determined before treatment initiation, as alterations in these 2 genes predict sensitivity towards cBTKi activity. Treatment approaches for WM-associated cryoglobulins, cold agglutinins, AL amyloidosis, Bing-Neel syndrome (BNS), peripheral neuropathy, and hyperviscosity syndrome follow the common principle of reducing tumor and abnormal protein burden rapidly and deeply to improve symptoms. In BNS, ibrutinib can be highly active and produce durable responses. In contrast, cBTKi are not recommended for treating AL amyloidosis. The panel emphasized that continuous improvement of treatment options for symptomatic, treatment-naïve WM patients critically depends on the participation of patients in clinical trials, whenever possible.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalSeminars in Hematology
Issue number2
StatePublished - Mar 2023
Externally publishedYes


  • BTK-inhibitors
  • CXCR4
  • Chemoimmunotherapy
  • MYD88
  • Treatment-naïve
  • Waldenstrom's Macroglobulinemia


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