BTK Inhibitor in Relapsed or Refractory Mantle Cell Lymphoma


Key Points

  • Acalabrutinib produced a response in 81% of patients, including a complete response in 40%.
  • The median duration of response was not reached.

A phase II study (ACE-LY-004) reported in The Lancet by Wang et al showed durable responses with the Bruton tyrosine kinase inhibitor acalabrutinib (Calquence) in patients with relapsed or refractory mantle cell lymphoma. The study supported the recent approval of acalabrutinib in this setting.

Study Details

In the multicenter study, 124 patients from 40 sites in 10 countries were enrolled between March 2015 and January 2016 and treated with oral acalabrutinib at 100 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response on the Lugano classification. The median age of patients was 68 years (65% aged ≥ 65 years), 80% were male, 24% had refractory disease, 75% had Ann Arbor stage IV disease, 73% had extranodal disease, and the median number of prior therapies was 2 (range = 1–2).


Median follow-up was 15.2 months. Response was achieved in 100 patients (81%), including a complete response in 49 (40%). Kaplan-Meier estimates of median durations of response, progression-free survival, and overall survival were not reached; the 12-month rates were 72%, 67%, and 87%, respectively. Median time to best response was 1.9 months, and median time to complete response was 3.4 months.

Adverse Events

The most common adverse events of any grade were headache (38%), diarrhea (31%), fatigue (27%), and myalgia (21%), and the most common grade ≥ 3 adverse events were neutropenia (10%), anemia (9%), and pneumonia (5%). One patient had grade 3 gastrointestinal hemorrhage. No atrial fibrillation was reported. Treatment-related serious adverse events occurred in 10% of patients. Treatment was discontinued in 6% due to adverse events.

The investigators concluded: “Acalabrutinib treatment provided a high rate of durable responses and a favourable safety profile in patients with relapsed or refractory mantle cell lymphoma. These findings suggest an important role for acalabrutinib in the treatment of this disease population.”

The study was funded by Acerta Pharma, a member of the AstraZeneca Group.

Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet article. 

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