by Dr. C.H. Weaver M.D. updated 6/2021
Brukinsa (zanubrutinib) monotherapy is generally well tolerated and active in the treatment of patients with of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) irrespective of 17p deletion status. Novel Brukinsa drug combinations look to further improve on treatment with single drugs.
Brukinsa is a Bruton tyrosine kinase (BTK) inhibitor. Within lymphoma cells, BTK is a protein/carbohydrate complex that is involved in maintaining cellular survival and replication. By inhibiting the activity of BTK, a BTK inhibitor reduces the growth of lymphoma cells and causes cellular death. Drugs that block BTK stop the flow of these growth signals causing lymphoma cells to die.
Doctors evaluated Brukinsa doses ranging from 40 mg to 160 mg twice daily or 320 mg once daily in a large group of patients with CLL/SLL. A total of 122 patients (average age, 67 years) were enrolled in this clinical trial including 117 with CLL and 5 with SLL.
With a median follow-up of 25.1 months, the overall response to treatment was 97% and the complete disappearance of cancer occurred in 14% of patients. Overall 97% and 89% of patients survived without CLL/SLL progression 1 and 2 years from treatment respectively.
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Brukinsa was well tolerated although some patients did experience contusion, upper respiratory tract infections, a low white blood cell count, cough, headache, and fatigue. Side effects resulted in a discontinuation rate of only 4% due.
The overall response to treatment and rate of survival without progression suggest this next generation BTK inhibitor can achieve deep and durable responses in patients with CLL/SLL. Research is ongoing to determine where it best fits in the overall management of CLL/SLL.
Brukinsa Compared to Imbruvica
The phase 3 ALPINE clinical trial compared Brukinsa to Imbruvica (ibrutinib) in patients with relapsed/refractory CLL/SLL who received at least 1 prior systemic therapy in 652 patients. The overall response to treatment with Brukinsa was 78% compared to 63% for Imbruvica and 95% of Brukinsa treated patients survived cancer free one year from treatment compared to 84% of those treated with Imbruvica. Overall survival and side effects were similar with both medications.2
- 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.
- Hillmen P, Eichhorst B, Brown JR, et al. First interim analysis of ALPINE study: Results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Presented at: 2021 European Hematology Association Congress; June 9-17, 2021; Virtual. Abstract LB190.