Zanubrutinib

Zanubrutinib is an oral targeted anticancer medicine belonging to the class of Bruton tyrosine kinase (BTK) inhibitors. BTK is an enzyme involved in B-cell receptor signalling, a pathway that supports the growth, survival and activity of certain B lymphocytes. By selectively inhibiting BTK, zanubrutinib interferes with signalling that can contribute to the development and persistence of particular B-cell malignancies. It is used in adults with certain blood cancers, including chronic lymphocytic leukaemia, small lymphocytic lymphoma, Waldenström’s macroglobulinaemia, mantle cell lymphoma, marginal zone lymphoma and selected cases of follicular lymphoma, depending on the applicable regulatory approval. It is taken orally as capsules or tablets, according to the prescribed product instructions. Treatment may be given alone or alongside another anticancer medicine, depending on the disease and treatment history. Zanubrutinib is generally continued until the disease progresses or adverse effects make continued treatment unsuitable, although the regimen depends on the indication. Because BTK inhibition can affect bleeding, immune defence, blood-cell counts and cardiac rhythm, patients require clinical assessment and monitoring throughout treatment. The approved indications, formulation instructions and dose adjustments may vary by country and product.

Zanubrutinib was developed as a selective BTK inhibitor to target B-cell signalling in haematological malignancies. The United States Food and Drug Administration (FDA) initially approved it in November 2019 for adults with mantle cell lymphoma who had received at least one previous therapy. Further US approvals expanded its use to Waldenström’s macroglobulinaemia, marginal zone lymphoma, chronic lymphocytic leukaemia or small lymphocytic lymphoma, and selected patients with follicular lymphoma in combination with obinutuzumab. The European Medicines Agency (EMA) granted marketing authorisation in the European Union in November 2021, with subsequent updates to the authorised indications. Key clinical development programmes include ASPEN in Waldenström’s macroglobulinaemia, SEQUOIA in previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma, and ALPINE in relapsed or refractory disease. The exact approved uses differ between jurisdictions, and some indications may have specific eligibility criteria or accelerated-approval conditions. Prescribers should verify the current local product information and applicable regulatory status before treatment.

Zanubrutinib is used in adults with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), and Waldenström’s macroglobulinaemia (WM). Depending on the country and product approval, it may also be indicated for mantle cell lymphoma (MCL) after previous treatment and for relapsed or refractory marginal zone lymphoma (MZL) following anti-CD20-based therapy. In the United States, zanubrutinib is also approved in combination with obinutuzumab for eligible adults with relapsed or refractory follicular lymphoma after at least two previous systemic treatment regimens. It is generally administered as monotherapy for several indications, while combination treatment is used for selected conditions. Treatment choice depends on the cancer subtype, previous therapies, disease characteristics, other medical conditions and local prescribing guidance.

Zanubrutinib is taken orally, with or without food. The usual adult dose is 160 mg twice daily or 320 mg once daily, depending on the prescribed regimen and applicable product information. Capsules should be swallowed whole with water and must not be opened, broken or chewed. Tablets should be handled according to their specific product instructions and should not be crushed or chewed. Treatment is generally continued until disease progression or unacceptable toxicity. Dose interruption or reduction may be necessary for certain adverse reactions, liver impairment or interactions with other medicines. Strong or moderate CYP3A inhibitors can increase zanubrutinib exposure and may require dose adjustment, while CYP3A-inducing medicines may need to be avoided. The prescribing clinician should select the appropriate regimen and review the current product-specific instructions before treatment begins.

Common side effects of zanubrutinib include reduced neutrophil and platelet counts, upper respiratory tract infections, bleeding or bruising, and musculoskeletal pain such as muscle or joint discomfort. Other reported effects include diarrhoea, fatigue, rash, cough and changes in blood-cell counts. Some patients may experience infections or require treatment adjustments because of laboratory abnormalities. The frequency and severity of adverse effects vary according to the patient's health, underlying cancer, treatment duration and concurrent medicines. Patients should report persistent or worsening symptoms to their healthcare professional rather than changing the dose independently.

Important risks associated with zanubrutinib include serious or opportunistic infections, significant bleeding, severe reductions in blood-cell counts and second primary malignancies, including skin cancers. Cardiac complications such as atrial fibrillation, atrial flutter and other arrhythmias have also been reported. Liver injury, including drug-induced liver injury, is another important safety concern. Treatment may need to be interrupted, reduced or discontinued if serious toxicity develops. Patients should promptly report unusual bleeding, black stools, persistent fever, breathing difficulties, palpitations, jaundice or other concerning symptoms. Clinicians should assess bleeding risk before surgery or invasive procedures and determine whether a temporary treatment interruption is appropriate. Zanubrutinib can cause fetal harm, so pregnancy-related precautions are necessary. Patients with serious hypersensitivity to the medicine or its ingredients should not receive it.

Before starting zanubrutinib, clinicians should review the patient's medical history, infection risk, bleeding history, cardiac conditions, liver function and current medicines. Baseline and periodic complete blood counts are important to detect cytopenias, while liver-function monitoring can help identify potential liver injury. Patients with a history of arrhythmias or cardiovascular disease may need additional assessment. Hepatitis B status and infection-prevention requirements should be reviewed where clinically appropriate, particularly in patients with previous infections or concurrent immunosuppressive treatment. Zanubrutinib is metabolised mainly through the CYP3A pathway, so strong or moderate CYP3A inhibitors may increase drug exposure, while CYP3A inducers can reduce exposure and potentially affect treatment effectiveness. Patients should inform their healthcare professional about all prescription medicines, non-prescription products and herbal supplements before starting or stopping any medicine. Pregnancy and breastfeeding require specific counselling, and effective contraception should be discussed when applicable. Vaccination plans should be reviewed in the context of the patient's immune status and cancer treatment.

Confirm the cancer diagnosis, treatment indication, previous therapies and locally approved regimen before prescribing zanubrutinib. Review baseline blood counts, liver function, infection history, bleeding risk and cardiovascular history. Perform a thorough medication reconciliation to identify CYP3A interactions, and reassess interactions whenever another medicine is started, stopped or changed. Counsel patients to follow the prescribed dosing schedule consistently and to take the medicine according to the instructions for their particular capsule or tablet formulation. Explain warning signs such as unusual bleeding, fever, palpitations and symptoms of liver injury, and provide clear instructions on when to seek medical attention. Coordinate treatment interruptions around surgery or invasive procedures with the treating oncology team. Continue periodic clinical and laboratory monitoring throughout therapy, and document dose changes and adverse reactions carefully.