News Report · Hematology

Zanubrutinib and Venetoclax Show Efficacy in CLL Treatment Algorithm: 80% ORR in ALPINE Trial

June 08, 2026

Overall Response Rate

80% in ALPINE trial

Clinical Perspective

The emergence of zanubrutinib as a potent BTK inhibitor with an 80% overall response rate in relapsed CLL patients signifies a potential shift in treatment strategies, particularly when combined with venetoclax.

Dr. Shruti Pandey · Hematology

Zanubrutinib (Brukinsa) achieved an overall response rate of 80% versus 73% for ibrutinib in the ALPINE trial for chronic lymphocytic leukemia (CLL) patients with relapsed or refractory disease [1]. This trial highlights the growing role of BTK inhibitors in the treatment landscape of CLL, particularly in combination with venetoclax.

Clinical Context

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow, characterized by the accumulation of abnormal lymphocytes. It is one of the most common leukemias in adults, with an estimated annual incidence of approximately 20,000 new cases in the United States. Current treatment options include chemotherapy and targeted therapies, such as BTK inhibitors and BCL-2 inhibitors. However, many patients experience disease progression or relapse after initial therapy, creating a significant need for effective treatment strategies. The recent approvals of zanubrutinib and venetoclax provide new options for managing CLL, particularly in patients who have not responded to prior therapies.

Key Findings

The ALPINE trial showed zanubrutinib achieved an overall response rate of 80% versus 73% for ibrutinib in patients with relapsed or refractory CLL (response rate ratio 1.10; 95% CI: 1.01, 1.20; p=0.0264) [1].
The trial enrolled 652 patients with relapsed or refractory CLL [1].
Event rates: 80% response in the zanubrutinib arm versus 73% in the ibrutinib arm [1].
The primary endpoint was overall response rate as determined by an independent review committee [1].
The median duration of response was not reached in either arm after a median follow-up of 14.1 months [1].
Zanubrutinib is administered at a dose of 160 mg orally twice daily or 320 mg once daily until disease progression or unacceptable toxicity [1].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Immune-mediated adverse reactions including pneumonitis colitis hepatitis endocrinopathies and nephritis reported with zanubrutinib — monitor throughout treatment and for at least 5 months after last dose [1].
Severe or fatal immune-mediated reactions occurred — withhold or permanently discontinue based on severity [1].
Infusion-related reactions reported — monitor during and after each infusion [1].
Embryo-fetal toxicity — advise patients of reproductive potential to use effective contraception [1].
Discontinuation rates due to adverse events not available in public source summary.
Complete adverse event profile available in the full prescribing information for zanubrutinib (Brukinsa) [1].

What This Means for Clinical Practice

Zanubrutinib is used in patients with relapsed or refractory chronic lymphocytic leukemia who have received prior therapies. The 80% overall response rate supports its use as a viable treatment option in this population. How this new data will influence treatment algorithms for CLL remains to be established?

Study Design

The ALPINE trial was a randomized, multicenter study that enrolled 652 patients with relapsed or refractory CLL. The primary endpoint was the overall response rate as assessed by an independent review committee with a median follow-up of 14.1 months. Key limitations of the study include potential biases in patient selection and the need for longer follow-up to assess long-term outcomes.

FAQ

What is zanubrutinib (Brukinsa) approved for?

Zanubrutinib is approved for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) as of January 19, 2023. This approval was based on the SEQUOIA trial demonstrating significant efficacy in treatment-naïve patients without 17p deletion.

How does zanubrutinib work?

Zanubrutinib is a selective Bruton’s tyrosine kinase (BTK) inhibitor that blocks the signaling pathways necessary for the survival and proliferation of B-cell malignancies. It differs from other BTK inhibitors by having a more selective binding profile, potentially leading to fewer off-target effects.

What is the recommended dose of zanubrutinib?

The recommended dose of zanubrutinib is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity. Clinicians should consult current prescribing information for full dosing guidance. Clinicians should consult the current label before prescribing.

What are the most common side effects of zanubrutinib?

Common adverse reactions associated with zanubrutinib include decreased neutrophil count (42%), upper respiratory tract infections (39%), and hemorrhage (30%). Serious adverse reactions and second primary malignancies have also been reported.

Zanubrutinib and Venetoclax Show Efficacy in CLL Treatment Algorithm: 80% ORR in ALPINE Trial

Zanubrutinib and Venetoclax Show Efficacy in CLL Treatment Algorithm: 80% ORR in ALPINE Trial

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

What This Means for Clinical Practice

Study Design

FAQ

References

Get weekly drug updates for Hematology in your inbox.

Related Drug Updates

FDA Approves Yartemlea for TA-TMA: First Treatment for Stem Cell Transplant Complication

FDA Approves Fitusiran for Hemophilia A and B: Antithrombin Lowering Mechanism Compared to Emicizumab

CAR-T Cell Therapy Shows Promising Outcomes for DLBCL and Multiple Myeloma in 2024

Verified HCP Portal