Brukinsa for treating certain adult lymphomas and leukemias

Brukinsa is an oral targeted cancer therapy that inhibits specific kinases and is used to treat adult patients with several types of lymphomas and leukemias. It is approved for mantle cell lymphoma, Waldenström's macroglobulinemia, relapsed or refractory marginal zone lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma, and in combination with obinutuzumab for relapsed or refractory follicular lymphoma after multiple prior treatments.

Brukinsa is indicated for treatment of adults diagnosed with:

• Mantle cell lymphoma (MCL) in patients who have received at least one prior therapy.
• Waldenström's macroglobulinemia (WM).
• Relapsed or refractory marginal zone lymphoma (MZL) after receiving at least one anti-CD20-based regimen.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Relapsed or refractory follicular lymphoma (FL), when used in combination with obinutuzumab, after two or more lines of systemic therapy.

Some indications have accelerated FDA approval based on response rates and require confirmation of clinical benefit in ongoing trials.

zanubrutinib

Brukinsa contains zanubrutinib, a Bruton tyrosine kinase (BTK) inhibitor. BTK is important for survival and proliferation of certain malignant B cells found in lymphomas and leukemias. By blocking BTK activity, Brukinsa disrupts the growth and survival signals in these cancer cells, helping to control the disease.

The usual recommended dose of Brukinsa for adults is either 160 mg orally twice daily or 320 mg orally once daily. It can be taken with or without food. Capsules should be swallowed whole and not opened, broken, or chewed. Tablets should also be swallowed whole or split in half if prescribed; they should not be chewed or crushed.

In patients with severe liver impairment (Child-Pugh class C), dose reduction to 80 mg twice daily is recommended. No adjustment is needed for mild or moderate hepatic impairment.

If a patient misses a dose, it should be taken as soon as possible on the same day, with the next dose given at the usual scheduled time.

Dose modifications may be needed when Brukinsa is taken with certain CYP3A inhibitors or inducers; strong CYP3A inducers should be avoided. Specific dose adjustments are recommended when used with drugs like clarithromycin and posaconazole. Dosage may also need to be reduced or interrupted for Grade 3 or higher adverse reactions, with guidelines provided for hematological and nonhematological toxicities.

No known contraindications have been specified for Brukinsa.

• Hemorrhage: Serious and sometimes fatal bleeding events, including intracranial hemorrhage, have occurred. About 3.8% of patients experienced Grade 3 or higher bleeding. Cautious use and monitoring are necessary, especially if combined with antiplatelet or anticoagulant therapy. Discontinue immediately if intracranial hemorrhage occurs.
• Infections: Fatal and serious infections including bacterial, viral, fungal, and opportunistic infections have been reported. Monitor for infection symptoms and consider prophylaxis in high-risk patients.
• Cytopenias: Significant decreases in neutrophils, platelets, and hemoglobin have been observed. Regular blood counts are essential for early detection and management.
• Second primary malignancies: Occur in about 14% of patients, including skin cancers and other solid tumors. Patients should use sun protection and be monitored.
• Cardiac arrhythmias: Atrial fibrillation/flutter and ventricular arrhythmias have been reported. Monitor for symptoms such as palpitations and dizziness, especially in patients with cardiac risk factors.
• Hepatotoxicity: Cases of drug-induced liver injury, including severe and fatal instances, have been reported. Liver function tests should be performed before and during treatment. Withhold or discontinue treatment if liver injury is suspected or confirmed.
• Embryo-fetal toxicity: Brukinsa can cause fetal harm. Women should avoid pregnancy during treatment and for one week after the last dose. Men are advised to avoid fathering a child during treatment and for one week after the last dose.

The most common side effects occurring in at least 30% of patients include decreased neutrophil counts, decreased platelet counts, upper respiratory tract infections, bleeding events, and musculoskeletal pain.

Less common but serious adverse effects include severe bleeding, infections, cytopenias, cardiac arrhythmias, liver injury, and second primary cancers.

Brukinsa is metabolized by CYP3A enzymes, so concomitant use with CYP3A inhibitors or inducers affects its levels.

• Moderate CYP3A inhibitors (e.g., clarithromycin 250 mg twice daily): reduce Brukinsa dose to 80 mg twice daily.
• Strong CYP3A inhibitors (e.g., clarithromycin 500 mg twice daily, posaconazole higher doses): reduce Brukinsa dose to 80 mg once daily.
• Strong CYP3A inducers should be avoided. If moderate inducers cannot be avoided, increase Brukinsa dose to 320 mg twice daily.
• After stopping CYP3A modulators, resume previous Brukinsa dose.

Pregnancy: Brukinsa may cause fetal harm based on animal data. Women should avoid pregnancy during treatment and for one week after the last dose.

Contraception: Both women and men should use effective contraception during treatment and for one week after the last dose.

Lactation: Information about use during breastfeeding is not provided.