BTK inhibitors are tablets that block a growth pathway of CLL cells. Ibrutinib was the first drug in this group, but it sometimes causes heart problems such as an irregular heartbeat. In this head-to-head comparison, zanubrutinib (a newer generation) controlled the disease for longer and caused fewer heart side effects.
Untreated or relapsed/refractory CLL/SLL; continuous treatment
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Zanubrutinib | 160 mg twice daily or 320 mg once daily | Oral, with or without food | Continuous |
Severe hepatic impairment (Child-Pugh C): 80 mg twice daily. With CYP3A inhibitors or inducers, adjust the dose according to the label.
On the page “Leukaemia” · Regimens and dosing in CLL: continuous BTK inhibitor therapy
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity.
Ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity.
Source of the regimen details: ClinicalTrials.gov NCT03734016 (dose and inclusion criteria)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with relapsed or refractory CLL or SLL after at least 1 prior systemic therapy, requiring treatment according to iwCLL 2008, with measurable disease on CT/MRI, ECOG 0 to 2 and adequate bone marrow, renal and hepatic function. Significant cardiovascular disease, a history of stroke or intracranial haemorrhage within the past 180 days and severe bleeding disorders were exclusion criteria.
Primary endpoint: overall response rate (superiority of zanubrutinib was shown in the interim analyses).
Key secondary endpoint: progression-free survival (hierarchical testing: first non-inferiority, then superiority).
The safety profile of zanubrutinib was better than that of ibrutinib: fewer discontinuations due to adverse events and fewer cardiac events, including cardiac events leading to treatment discontinuation or death.
ALPINE was the first study to show the superiority of one BTK inhibitor over another in terms of progression-free survival. Zanubrutinib (Brukinsa) was approved by the FDA in 2023 for CLL/SLL (untreated and relapsed). Second-generation BTK inhibitors (zanubrutinib and acalabrutinib) have largely replaced ibrutinib in clinical practice because of better cardiac safety.
The study was open-label. Progression-free survival was the key secondary (not primary) endpoint. Patients had not previously received a BTK inhibitor, so the results cannot be generalised to BTK-resistant patients. The study was sponsored by the manufacturer of zanubrutinib.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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