A phase II study (ACE-LY-004) reported in The Lancet by Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, and colleagues 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.
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, 24% had refractory disease, 75% had Ann Arbor stage IV disease, 73% had extranodal disease, and the median number of prior therapies was 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.
The most common adverse events 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%). Treatment-related serious adverse events occurred in 10% of patients, which led to treatment discontinuation in 6%.
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.”