Up-to-date Information on
Waldenström’s macroglobulinemia


Phase II – Tirabrutinib

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

Phase II study of tirabrutinib for Waldenström’s macroglobulinemia

Study design

  • The trial was conducted with an open‐label and single‐arm design at 19 sites in Japan
  • Inclusion criteria in Cohort A
    • Presence of symptomatic WM or serum IgM levels of >4000 mg/dL
  • Other major eligibility criteria for both cohorts
    • Age ≥ 20 years
    • Monoclonal gammopathy with serum IgM levels of >500 mg/dL
    • An Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
    • Acceptable laboratory test results
  • Major exclusion criteria
    • Tumor lesions in the central nervous system (CNS) and prior administration of BTK inhibitors
  • Patients were treated with tirabrutinib 480 mg once daily orally under fasting conditions for 28 days as 1 cycle
  • Tirabrutinib was continued until disease progression or clinically unacceptable toxicity


Figure 1. Study design: Phase II study of <a href='/glossary/tirabrutinib/' class='glossary' title='tirabrutinib'>tirabrutinib</a> in patients with Waldenström’s macroglobulinemia

Figure 1: Study design of the phase II tirabrutinib study. Derived from Sekiguchi N, et al. Cancer Sci. 2020;111(9):3327-3337.1

Patient population

  • Median age was 71 years
  • Median serum immunoglobulin M (IgM) level was 3600 mg/dL
  • The MYD88L265P mutation was present in 96.2% of patients



  • MRR and ORR were 88.9% and 96.3%, respectively (Figure 2)
  • Median time to major response was 1.87 months


  • PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 months for Cohorts A and B, respectively


  • The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%)
  • Most AEs were classified as grade 1 or 2
  • Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%)
  • No grade 5 AEs were noted
  • All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension.

Figure 2. Median response rate (MRR) and overall response rate (ORR)

Figure 2. Median response rate (MRR) and overall response rate (ORR). Derived from Sekiguchi N, et al. Cancer Sci. 2020;111(9):3327-3337.1


  • Although the follow‐up duration was relatively short, the study met the primary endpoint (major response rate).
  • The present study demonstrated that tirabrutinib monotherapy is highly effective with rapid responses and is well tolerated in both treatment-naïve patients and those with relapsed / refractory symptomatic WM.
  • Some efficacy endpoints (including PFS and OS) could not be evaluated due to the limited observation period; therefore, future studies with a longer follow‐up period are warranted.



1.Sekiguchi N, Rai S, Munakata W, et al. A multicenter, open-label, phase II study of tirabrutinib (ONO/GS-4059) in patients with Waldenström’s macroglobulinemia. Cancer Sci 2020:111(9);3327-3337.
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