Zanubrutinib in CLL: The ALPINE Trial

EP: 1.Disease Overview: Mantle Cell Lymphoma

EP: 2.Factors for Consideration in Treatment Decision-making for MCL

EP: 3.Mantle Cell Lymphoma Maintenance Strategies

EP: 4.Second-line Therapies in MCL: Regimens With BTK Inhibitors and BCL-2 Targeting Therapies

EP: 5.BTK Inhibitors in Relapsed/Refractory MCL and Treatment Selection

EP: 6.CAR T-Cell Therapy in R/R MCL

EP: 7.Strategies for Sequencing and Combining Therapies in MCL

EP: 8.Advancements on the Horizon in Mantle Cell Lymphoma

EP: 9.Treatment Overview: Chronic Lymphocytic Leukemia

EP: 10.Acalabrutinib in CLL: Insights from the ELEVATE TN and ASCEND Trials

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EP: 11.Zanubrutinib in CLL: The ALPINE Trial

EP: 12.Treatment Decision-making Among Second-generation BTKis in CLL

EP: 13.Updates from Patient-reported QOL and Matching-adjusted Indirect Treatment Comparisons (MAICs) Studies in CLL

EP: 14.Emerging Approaches in CLL

EP: 15.TRANSCEND CLL: CAR T-cell Therapy for CLL

EP: 16.The Potential Role of Venetoclax Combination Approaches in CLL

EP: 17.Considerations for COVID-19 in MCL and CLL

EP: 18.Anti-CD20 Regimens and Triplet Therapies in CLL

EP: 19.Pirtobrutinib and Other Non-Covalent BTK Inhibitors in the Treatment of CLL

EP: 20.Closing Remarks on Upcoming Data and Future Perspectives in MCL and CLL

Anthony R. Mato, MD, MSCE: I want to switch gears now and talk about zanubrutinib. Alexey, we have some longer-term follow-up data for zanubrutinib that was presented at EHA (European Hematology Association) [2022 Congress]. Can you comment on that and share your thoughts about the molecule in general?

Alexey V. Danilov, MD, PhD: I guess we still call them second-generation [agents], [but] zanubrutinib is a more selective BTK (Bruton tyrosine kinase) inhibitor. It has been really coming fast and furious with multiple randomized trials. This is probably one of the longest rollouts that we've had through zanubrutinib in a phase 2 trial in relapsed/refractory CLL (chronic lymphocytic leukemia), presented at EHA. The overall response rate there was essentially 90% to 100%. The follow-up was about 3 years, [and] progression-free survival was about 70% at the 3-year mark. The discontinuation rate for adverse events was about 15%, which compares somewhat favorably with ibrutinib. Overall, there were some of the same adverse events that we see with ibrutinib, including atrial fibrillation and hypertension. However, as you know, there have been other studies that directly compared zanubrutinib with ibrutinib in CLL and Waldenstrom macroglobulinemia, suggesting that the adverse event profile is much more favorable with this drug. It will certainly be an important drug in the market for CLL, and it's already incorporated into NCCN (National Comprehensive Cancer Network) guidelines.

Anthony R. Mato, MD, MSCE: Can you give a comment on how zanubrutinib compares with ibrutinib from the perspective of the head-to-head comparison?

Catherine C. Coombs, MD: [The] ALPINE [trial] (NCT03734016) is the head-to-head trial of ibrutinib with zanubrutinib. It was a little different from the trial comparing acalabrutinib with ibrutinib, which focused on patients [with] high-risk [disease]. This trial took all comers in the relapsed setting, so it was not specifically focused on patients [with] high-risk [disease]. The other big difference is that its primary outcome was overall response rate as a composite of PR (partial response) and CR (complete response). Nevertheless, it was a positive study in that it actually showed that zanubrutinib had a superior overall response rate as compared with ibrutinib. It also looks like there may be improved progression-free survival; however, the caveat is that the follow-up on this trial is very short. It's a little over 1 year.

It was also a very nice comparator between the head-to-head toxicity profiles of these 2 drugs. One of the exciting things about zanubrutinib is that it has, so far, very low rates of atrial fibrillation [and] flutter. [In] that trial, it was 2.5% compared with ibrutinib's 10%, so we'll see what happens with longer-term follow-up. As far as other toxicities go, zanubrutinib has very similar rates of hypertension as compared with ibrutinib. They both were about 16% in each arm. There is a little bit more neutropenia with the zanubrutinib, although I'll say in my own practice, I don't think it's usually very clinically significant. Overall, a favorable look at zanubrutinib, but it had a short follow-up, so we'll need a few more years before making any firm conclusions on that one.

Transcript has been edited for clarity.