Up-to-date Information on
Waldenström’s macroglobulinemia


PHASE II – Acalabrutinib

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

Phase II study of acalabrutinib for Waldenström’s macroglobulinemia

Study design

  • In this single‑arm phase II study of acalabrutinib in patients with Waldenström's macroglobulinemia, 106 treatment-naïve or relapsed or refractory patients received 100 mg acalabrutinib twice a day (6 patients received 200 mg once a day but later switched 100 mg twice a day) in 28‑day cycles until progressive disease or intolerance.1


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

Figure 1: Study design of the phase II acalabrutinib study. Derived from Owen RG, et al. Lancet Haemotology. 2020. 7(2):E112-E121.1



  • After a median follow-up of 27·4 months the overall response rate was 93%, with a major response occurring in 78% to 80% of patients
  • Progression-free survival (PFS) with acalabrutinib at 24‑month follow-up was 90% in treatment-naïve patients and 82% in the relapsed or refractory group.
  • The overall survival was 92% in treatment-naïve patients and 89% in relapsed or refractory patients, in the same time period

A review of a phase II study in patients with Waldenström's macroglobulinemia

Figure 2: Response rates in patients receiving acalabrutinib. Derived from Owen RG, et al. Lancet Haemotology. 2020. 7(2):E112-E121.1


  • Common adverse events of any grade were headache, diarrhea, contusion, and dizziness. Common grade 3 and 4 adverse events were neutropenia, pneumonia, anemia, increased alanine aminotransferase, and hyponatremia.
  • Of note, bleeding events occurred in 58% of patients and were commonly contusion (29%) and epistaxis (11%).
  • Atrial fibrillation occurred in 5 patients and grade 3 hypertension occurred in 3 patients.1

Common adverse events – Waldenström's macroglobulinemia

Figure 3: Common adverse events. Derived from Owen RG, et al. Lancet Haemotology. 2020. 7(2):E112-E121.1


  • This present study demonstrated that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström’s macroglobulinemia.
  • Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies.


1.Owen, RG, McCarthy, H, Rule, et al. Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study. Lancet Haemotology 2020: 7(2);E112-E121.