From the Guidelines
Zanubrutinib has demonstrated superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients, with a hazard ratio of 0.42 compared to bendamustine-rituximab CIT in the SEQUOIA trial 1.
Key Findings
- The SEQUOIA trial showed that continuous zanubrutinib had a significantly longer PFS compared to bendamustine-rituximab CIT in older patients with CLL, with a two-sided P value of less than 0.0001 1.
- Zanubrutinib has been approved by the EMA and FDA for first-line therapy of CLL based on the results of the SEQUOIA trial 1.
- The study highlights the importance of optimal patient counseling, including information on the related risk of developing myeloid neoplasias, and pre-treatment evaluation to assess IGHV and TP53 status, deletions in chromosome 17p, and patient-related factors such as comedication and comorbidities 1.
Treatment Considerations
- Zanubrutinib is a selective Bruton's tyrosine kinase (BTK) inhibitor that disrupts B-cell receptor signaling pathways critical for CLL cell survival and proliferation.
- The standard dosing for zanubrutinib is 160 mg twice daily, taken orally with or without food.
- Regular monitoring for side effects such as neutropenia, infections, and bleeding is recommended during treatment.
Patient Outcomes
- Zanubrutinib has shown excellent PFS and complete response rates in CLL patients, with 24-month PFS rates exceeding 85% across patient populations.
- Complete response rates range from approximately 6-15%, which is notable for BTK inhibitor therapy where partial responses are more common.
- Zanubrutinib's efficacy extends to high-risk CLL patients, including those with del(17p) and TP53 mutations.
From the Research
Progression-Free Survival
- The progression-free survival (PFS) benefit of zanubrutinib over ibrutinib was sustained in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, with a hazard ratio (HR) of 0.68 (95% confidence interval [CI], 0.54-0.84) at a median follow-up of 42.5 months 2.
- Zanubrutinib was found to be superior to ibrutinib with respect to PFS among 652 patients, with an HR for disease progression or death of 0.65 (95% CI, 0.49 to 0.86; P = 0.002) at a median follow-up of 29.6 months 3.
- The 24-month PFS rates were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group 3.
Complete Response Rate
- The complete response/complete response with incomplete bone marrow recovery rates were 11.6% with zanubrutinib and 7.7% with ibrutinib at a median follow-up of 42.5 months 2.
- The overall response rate (ORR) was significantly higher with zanubrutinib (85.6%) compared to ibrutinib (75.4%) 2.
- The ORR was higher with zanubrutinib (78.3%) versus ibrutinib (62.5%) at a median follow-up of 15 months 4.
Subgroup Analysis
- In patients with del(17p)/TP53 mutation, zanubrutinib had a longer PFS than ibrutinib, with an HR for disease progression or death of 0.53 (95% CI, 0.31 to 0.88) 3 and 0.51 (95% CI, 0.33-0.78) 2.
- Zanubrutinib had a higher ORR than ibrutinib in subgroups with del(17p)/TP53 mutations (80.5% vs 50.0%) and del(11q) (83.6% vs 69.1%) 4.