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 (TN) or relapsed or refractory patients (R/R) 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.1,2,3


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 (ORR) was 93%, with a major response occurring in 78% to 80% of patients as per both the 6th IWWM criteria and the modified 3rd IWWM criteria
  • Response by MYD88 mutational status was assessed in 50 patients, which included 36 MYD88L265P (34 R/R and and two TN) and 14 MYD88WT (13 R/R and one TN) patients
  • The ORR was 94% in the MYD88L265P patients and 79% in the MYD88WT patients with a major response occurring in 78% of MYD88L265P patients and 57% of MYD88WT patients as per both criteria1
  • PFS with acalabrutinib at 24‑month follow-up was 90% in treatment-naïve patients and 82% in the relapsed or refractory group.
  • The OS was 92% in treatment-naïve patients and 89% in relapsed or refractory patients, in the same time period1

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.
2.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.
3.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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