Zanubrutinib Shows High Overall Response Rate and Durable Responses in CLL and SLL

A global clinical trial called AU-003 was conducted in patients with various B-cell cancers. Patients received doses of zanubrutinib that ranged from 40 mg once daily to the final recommended dose, 160 mg twice daily or 320 mg once daily. Zanubrutinib was given until progression of the cancer or until toxicity was unacceptable. At ASH 2019, researchers reported data from 123 patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) who had not received prior Bruton tyrosine kinase (BTK) therapy (such as ibrutinib). Key end points in this study were response rates and progression-free survival (PFS).

Zanubrutinib trials allow use of anticoagulant and antiplatelet agents, as well as proton pump inhibitors and other gastric acid-reducing agents.

As of December 2018, 118 patients with CLL and 5 patients with SLL received zanubrutinib. The most common side effects were bruising (46%), upper respiratory tract infection (39%), diarrhea (30%), cough (28%), headache (23%), and fatigue (20%). Severe side effects were low white blood-cell count (15%), pneumonia (12%), and anemia (6%). Zanubrutinib treatment was discontinued because of side effects in 4% of patients. One patient died on study due to an unrelated cause.

Of the 123 evaluable patients, including patients who were enrolled for at least 3 months prior to data analysis, 22 were previously untreated and 101 had relapsed/refractory CLL. After median follow-up of 30 months, the overall response rate was 96%. Complete responses (CR), including CR with incomplete bone marrow recovery, were seen in 15% of patients. The response rate was similar in patients with relapsed/refractory CLL.

At 1 year, 95% of patients receiving zanubrutinib were progression-free. At 2 years, this rate was 95% for patients who had not received prior treatment and 91% for patients who had received prior therapy for CLL. Median PFS has not been reached.

Among patients with higher-risk CLL based on the presence of del(17p), the overall response rate was 94%. At 2 years, 75% of these patients were progression-free.

Researchers concluded that these data suggest that zanubrutinib was well-tolerated and active in patients with CLL/SLL, regardless of their 17p deletion status. Efficacy data, including 2-year PFS rates, suggest that this next-generation BTK inhibitor can achieve deep and durable responses in patients with CLL/SLL.

Abstract 500. ASH 2019.