From the Guidelines
Zanubrutinib demonstrates excellent progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients, with a hazard ratio of 0.42 compared to bendamustine-rituximab CIT in older patients, as shown in the SEQUOIA trial 1.
Key Findings
- The SEQUOIA trial compared continuous zanubrutinib with bendamustine-rituximab CIT in older patients and reported a PFS hazard ratio of 0.42, with a 95% CI of 0.28-0.63, and a two-sided P < 0.0001 1.
- Zanubrutinib has been approved by the EMA and the FDA in first-line therapy of CLL based on the results of the SEQUOIA trial 1.
- The study suggests that zanubrutinib is a valuable treatment option for CLL patients, particularly in the first-line setting.
Treatment Considerations
- Zanubrutinib is typically administered continuously until disease progression or unacceptable toxicity.
- The drug's improved PFS outcomes are attributed to its more complete and sustained BTK inhibition with fewer off-target effects compared to first-generation BTK inhibitors.
- Zanubrutinib's safety profile is favorable, with lower rates of cardiovascular adverse events, particularly atrial fibrillation and hypertension, which can lead to fewer treatment discontinuations and better long-term disease control.
Patient Selection
- Pre-treatment evaluation should include assessment of IGHV and TP53 status, deletions in chromosome 17p, and patient-related factors such as comedication, comorbidities, preference, drug availability, and expected treatment adherence 1.
- Zanubrutinib may be considered for patients with CLL, particularly those with del(17p), as it has shown superior PFS compared to bendamustine-rituximab CIT in older patients.
From the FDA Drug Label
The median PFS (95% CI), months#NE (34.3, NE)35 (33.2,44.3) Rate at 12 months, % (95% CI)¶92 (87,95)86 (80,91) Rate at 18 months, % (95% CI)‡95 (88,98)
The progression-free survival of zanubrutinib in Chronic Lymphocytic Leukemia (CLL) at 12 months is 92% (87,95) and at 18 months is 95% (88,98). The median PFS is not estimable, but it is at least 34.3 months. 2
From the Research
Progression-Free Survival of Zanubrutinib in Chronic Lymphocytic Leukemia (CLL)
- The progression-free survival of zanubrutinib in CLL has been evaluated in several studies, including the SEQUOIA trial 3, the ALPINE trial 4, 5, and a pooled analysis of three studies 6.
- In the SEQUOIA trial, zanubrutinib significantly improved progression-free survival compared to bendamustine-rituximab, with a hazard ratio of 0.42 (95% CI 0.28-0.63) 3.
- The ALPINE trial demonstrated that zanubrutinib had a longer progression-free survival compared to ibrutinib, with a hazard ratio of 0.65 (95% CI 0.49-0.86) 4 and 0.68 (95% CI 0.54-0.84) in the final comparative analysis 5.
- A pooled analysis of three studies found that zanubrutinib yielded long-term benefits and demonstrated a favorable safety profile for patients with CLL, with progression-free survival significantly longer in the treatment-naive group and the group with only one prior line of therapy 6.
Key Findings
- Zanubrutinib has shown significant improvement in progression-free survival compared to other treatments, including bendamustine-rituximab and ibrutinib.
- The median progression-free survival was not reached in the zanubrutinib group in the SEQUOIA trial, and the hazard ratio for disease progression or death was 0.42 (95% CI 0.28-0.63) 3.
- In the ALPINE trial, the median progression-free survival was not reported, but the hazard ratio for disease progression or death was 0.65 (95% CI 0.49-0.86) 4 and 0.68 (95% CI 0.54-0.84) in the final comparative analysis 5.
Safety Profile
- The safety profile of zanubrutinib has been evaluated in several studies, including the SEQUOIA trial 3, the ALPINE trial 4, 5, and a pooled analysis of three studies 6.
- The most common adverse events associated with zanubrutinib include infections, neutropenia, and thrombocytopenia 3, 6.
- The incidence of atrial fibrillation/flutter was lower with zanubrutinib compared to ibrutinib in the ALPINE trial 4, 5.