Zanubrutinib Demonstrates Efficacy and Tolerability Among BTK Inhibitor Intolerant Patients With CLL/SLL

Zanubrutinib demonstrated durable disease control and improved tolerability among patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) previously intolerant to ibrutinib and/or acalabrutinib, according to study results published in Blood Advances.  

Previous research has found zanubrutinib, a selective next-generation Bruton tyrosine kinase (BTK) inhibitor, efficacious for the treatment of CLL/SLL. Researchers conducted the ongoing phase 2 BGB-3111-215 study to determine the safety and tolerability of zanubrutinib among patients refractory to ibrutinib and/or acalabrutinib.

The primary end point was safety of zanubrutinib compared to ibrutinib- or acalabrutinib-intolerance adverse events. Secondary end points were overall response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS).

Overall, 71 patients were included and treated with zanubrutinib, of which 68% received 160 mg BID and 32% received 320 mg QD. All included patients reported prior intolerance to ibrutinib (n = 44), acalabrutinib (n = 17), or both (n = 10).

Among ibrutinib-intolerant patients, 54% had no recurrence of adverse events on while taking zanubrutinib. The most common adverse events to recur were fatigue (64%), rash (56%), hemorrhage (890%), and arthralgia (50%).

Additionally, 70% of acalabrutinib-intolerant patients experienced no recurrence of intolerance adverse events. The most common adverse event to recur was diarrhea (100%).Treatment-emergent adverse events with zanubrutinib were reported among 96% of patients, with the most common being fatigue (32%), COVID-19 (28%), diarrhea (24%), and contusion (24%). Grade 3 or higher treatment-emergent adverse events with zanubrutinib were reported among 61% of patients, with the most common being neutropenia (`3%), pneumonia (7%), COVID-19 (6%), and hypertension (6%).

Among 67 efficacy-evaluable patients, 94% achieved disease control, including 30% with stable disease and 64% with partial or complete responses. At 2 years, the DOR event-free rate was 79% (95% confidence interval [CI], 62 to 89) and the PFS event-free rate was 76% (95% CI, 62 to 85).

"These data suggest that zanubrutinib may be an alternative treatment option for patients with CLL/SLL who are intolerant of ibrutinib or acalabrutinib,” the researchers concluded.

Source:

Shadman M, Burke JM, Cultrera J, et al. Zanubrutinib is well tolerated and effective in CLL/SLL patients intolerant of ibrutinib/acalabrutinib: Updated results. Blood Advances. Published online May 7, 2025. doi:10.1182/bloodadvances.2024015493