Up-to-date Information on
Waldenström’s macroglobulinemia


Phase II – Venetoclax

Learn more about the latest clinical trials in Waldenström’s macroglobulinemia.

Phase II study of venetoclax for Waldenström’s macroglobulinemia

Study design

  • In a multicenter phase 2 clinical trial evaluating venetoclax in patients with Waldenström’s macroglobulinemia, 32 patients were enrolled.1
  • The median number of prior therapies was 2 (range 1-10), and 16 patients were previously treated with a BTKi. All patients carried the MYD88L265P mutation and 17 also had a CXCR4 mutation.2,3,4,5

Phase II <a href='/glossary/venetoclax/' class='glossary' title='Venetoclax'>Venetoclax</a> Study Design: Waldenström's macroglobulinemia

Figure 1: Study design of the phase II venetoclax study. Derived from Castillo J, et al. Clinical Lymphoma, Myeloma and Leukemia 2019; 19 (10) Supp E39-E40​2



  • The overall response rate (ORR) was 84% which included very good partial response (VGPR 6,7), partial response (PR 8,9), and minor response (MR, [n=1, 3%) with no patient attaining a complete response
  • The overall response rate was lower in those with refractory versus relapsed disease (60% vs 95%, p=0.03) and patients who received ≥ 3 vs < 3 prior lines of therapy (63% v 95%, p=0.04)
  • A major response rate (MRR) of 81% was observed across all patients and was significantly lower in those with refractory versus relapsed disease (50% vs 95%, p=0.07)
  • Prior BTKi exposure and CXCR4 mutational status were not associated with a lower ORR or MRR
  • The median time to minor and major responses was 1.9 and 5.1 months respectively. Previous exposure with BTKis was associated with a longer time to response (4.5 vs 1.4 months, p<0.01)

Progression-free survival (PFS) and overall survival (OS)

  • The 12- and 24-month PFS rates were 83% and 80% respectively
  • All 32 patients were alive at the time of data cutoff, for a 30-month OS of 100%


  • Generally the treatment was well-tolerated
  • Thirty-one patients (94%) experienced a grade ≥ 2 adverse event
  • The only grade 4 adverse events were neutropenia (n=6) and febrile neutropenia (n=1). All patients received G-CSF, and all events were resolved with a median of 4 days (range, 0-17 days)
  • Laboratory tumor lysis without clinical sequelae occurred in one patient


VGPR depends on prior BTKi treatment and CXCR4 mut status

Figure 2: Derived from Castillo J, et al. J Clin Oncology 2021; 40:63-713



  • Venetoclax is safe and highly active in patients with previously treated WM, including those previously treated with BTKis.
  • CXCR4 mutation status did not affect treatment response.
  • A study combining ibrutiniband venetoclaxin previously untreated patients with Waldenström macroglobulinemia is ongoing (NCT04273139)
  • ibrutiniband venetoclaxin previously untreated patients with Waldenström macroglobulinemia is ongoing (NCT04273139)



1.Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia. N Engl J Med. 2018: 378;2399-2410.
2.Boross P and Leusen JHW. Mechanisms of action of CD20 antibodies. Am J Cancer Res 2012: 2(6);676-690
3.Castillo JJ, Allan JN, Siddiqi T, et al. Venetoclax in Previously Treated Waldenström Macroglobulinemia. Journal of Clinical Oncology 2022: 40(1);63-71.
4.Acalabrutinib on ClinicalTrials.gov An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström Macroglobulinemia. Available from; https://clinicaltrials.gov/ct2/show/NCT02180724. Accessed February 12th, 2022.
5.Acalabrutin in the EU clinical trials register An Open-label, Phase 1b/2 Study of ACP-196 in Subjects with Waldenström Macroglobulinemia. Available from; https://www.clinicaltrialsregister.eu/ctr-search/search?query=Acalabrutinib+waldenstrom. Accessed February 12th, 2022
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