What is the median Progression-Free Survival (PFS) with zanubrutinib (Bruton's tyrosine kinase inhibitor) in Chronic Lymphocytic Leukemia (CLL)?

From the Guidelines

The median progression-free survival (PFS) with zanubrutinib in chronic lymphocytic leukemia (CLL) has not been explicitly stated in the provided evidence, but based on the SEQUOIA trial, zanubrutinib demonstrated a significantly improved PFS compared to bendamustine-rituximab, with a hazard ratio of 0.42, indicating excellent long-term disease control 1.

Key Points

• Zanubrutinib is a third BTKi approved by the EMA and FDA for first-line therapy of CLL, based on the results of the SEQUOIA trial 1.
• The SEQUOIA trial compared continuous zanubrutinib with bendamustine-rituximab CIT in older patients, showing a significantly improved PFS for zanubrutinib, with a hazard ratio of 0.42, and a two-sided P < 0.0001 1.
• While the exact median PFS with zanubrutinib is not provided, the trial results indicate a substantial benefit in terms of disease control, making zanubrutinib a valuable treatment option for CLL patients.

Clinical Implications

• The improved PFS with zanubrutinib translates to better morbidity and mortality outcomes for CLL patients, as well as an improved quality of life due to delayed disease progression.
• The use of zanubrutinib in clinical practice should be guided by patient-specific factors, including comorbidities, preference, and expected treatment adherence, as well as the results of pre-treatment evaluations, such as IGHV and TP53 status assessments 1.

From the Research

Median PFS with Zanubrutinib in CLL

• The median PFS with zanubrutinib in CLL is not explicitly stated in the provided studies, but the SEQUOIA study showed that zanubrutinib significantly prolonged progression-free survival (PFS) when compared to bendamustine-rituximab (BR) in treatment-naive CLL patients 2.
• The ALPINE trial demonstrated that zanubrutinib had a sustained PFS benefit compared to ibrutinib, with a hazard ratio of 0.68 (95% CI, 0.54-0.84) at a median follow-up of 42.5 months 3.
• The 12-month progression-free survival in the ALPINE trial was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69) 4.
• The studies suggest that zanubrutinib has improved efficacy and safety outcomes compared to ibrutinib, but the exact median PFS values are not provided 2, 3, 4.

Comparison with Ibrutinib

• Zanubrutinib had a higher overall response rate (ORR) compared to ibrutinib, with an ORR of 78.3% (95% CI, 72.0 to 83.7) versus 62.5% (95% CI, 55.5 to 69.1) at 15 months of median follow-up 4.
• Zanubrutinib also had a lower rate of atrial fibrillation compared to ibrutinib, with a rate of 2.5% versus 10.1% 4.
• The ALPINE trial demonstrated that zanubrutinib had a lower rate of cardiac events and major hemorrhages compared to ibrutinib 3, 4.

Clinical Implications

• The improved efficacy and safety profile of zanubrutinib compared to ibrutinib may make it a preferred treatment option for patients with CLL 2, 3, 4.
• The results of the ALPINE trial and other studies suggest that zanubrutinib may replace first-generation BTK inhibitors as a preferred therapeutic option for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile 2.