Orlando, Florida—At the 2019 ASH Annual Meeting, Constantine S. Tam, MBBS, MD,Royal Melbourne Hospital, Parkville, Victoria, Australia, presented data following-up on previous studies showing that zanubrutinib achieved complete and sustained BTK occupancy in peripheral blood mononuclear cells and lymph nodes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

According to Dr Tam et al, these new data detail zanubrutinib safety and efficacy data in a larger cohort of patients with CLL/SLL, with an additional 12 months of follow-up. A total of 122 patients (average age, 67 years) were enrolled in this phase 1/2 study, including 117 with CLL and 5 with SLL. 

Treatment consisted of zanubrutinib doses ranging from 40 mg to 160 mg twice daily or 320 mg once daily. The primary end point of the study was safety and tolerability, and secondary end points included rates of response and progression-free survival (PFS).  

With a median follow-up was 25.1 months, the overall response rate (ORR) was 97% and complete response rate was 14%. Notably, the ORR was comparable between treatment-naïve patients and those with relapsed/refractory disease. The PFS rate at 1 and 2 years was 97% and 89%, respectively.

The most common adverse events experienced with zanubrutinib were contusion, upper respiratory tract infection, neutropenia, cough, headache, and fatigue. The investigators also noted that the most common serious adverse events were pneumonia and urinary tract infections, with Dr Tam stating during the 2019 ASH presentation that “the treatment was well-tolerated despite very high drug levels, with a discontinuation rate of only 4% due to adverse events."

“These data suggest that zanubrutinib monotherapy was generally well tolerated and active in the treatment of patients with CLL/SLL irrespective of 17p deletion status,” said Dr Tam et al.

“The ORR, CRR [complete response rates], and 2-year PFS rates suggest this next generation BTK inhibitor can achieve deep and durable responses in patients with CLL/SLL,” they concluded.—Kaitlyn Manasterski

Cull Gavin, Simpson David, et al. Treatment with the Bruton Tyrosine Kinase Inhibitor Zanubrutinib (BGB-3111) Demonstrates High Overall Response Rate and Durable Responses in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Updated Results from a Phase 1/2 Trial. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 500.