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, 31 patients were enrolled.
  • 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.

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​



IgM, bone marrow involvement and hemoglobin levels

  • At baseline, median serum IgM was 3,542 mg/dl (range 642-7,970 mg/dl), median bone marrow involvement was 40% (range 4-95%) and median hemoglobin was 10.6 g/dl (range 6.4-13.5 mg/dl).
  • At 12 months, serum IgM declined to 1,071 mg/dl (range 89-4,770 mg/dl), bone marrow involvement declined to 3% (range 0-50%) and hemoglobin increased to 13.1 g/dl (range 8.9-14.9 g/dl).1


  • At best response, very good partial response was attained in 6 patients (19%), partial response in 19 (61%), minor response in 2 (6%), stable disease in 3 (10%) and no response in 1 (3%) (Figure 2).
  • The overall response rate was ≈87% and major response rate was ≈81% (rounded values may differ).
  • Patients with refractory disease had lower major response rate than patients with relapsed disease (p≤0.005).
  • Median time to respond (TTR) was 1.9 months (95% CI 1.1-3.1 months) and was slower in patients with prior BTKi exposure (p<0.001).1

Progression-free survival

  • The 2-year PFS rate is 76% (95% CI 52-89%).
  • Refractory disease was associated with a worse 2-year PFS (p≤0.003).1


  • Generally, the treatment was well tolerated.
  • Grade 4 neutropenia occurred in 5 patients.
  • Grade 3 adverse events included neutropenia (n=15), anemia (n=4) and diarrhea (n=4).
  • One instance of laboratory TLS occurred.
  • Venetoclax was dose reduced due to neutropenia (n=2), fatigue (n=1), diarrhea (n=1) and self-reduction (n=1).
  • No IgM flare or clinical TLS were observed, and there have been no deaths.1


VGPR depends on prior BTKi treatment and CXCR4 mut status

Figure 2: At best reponse. Derived from Castillo J, et al. Clinical Lymphoma, Myeloma and Leukemia 2019; 19 (10) Supp E39-E40


  • Venetoclax is a safe and effective treatment option for patients with symptomatic, previously treated WM.
  • A study combining ibrutinib and venetoclax in previously untreated patients with Waldenström macroglobulinemia is ongoing (NCT04273139).



1.Castillo J, Allan J and Siddiqui T. Multicenter Prospective Phase II Study of Venetoclax in Patients with Previously Treated Waldenstrom Macroglobulinemia. Clinical Lymphoma, Myeloma and Leukemia 2019: 19(10);Supp E39-E40