Can pleural effusion be reduced or cleared with Brukinsa (Zanubrutinib)?

Brukinsa (Zanubrutinib) and Pleural Effusion Management

Brukinsa (zanubrutinib) does not reduce or clear pleural effusions; in fact, it can cause hemorrhagic pleural effusion as a rare but serious adverse event and should be discontinued if pleural effusion develops. 1

Critical Safety Concern

Zanubrutinib has been reported to cause recurrent spontaneous hemorrhagic pleural effusion in patients with chronic lymphocytic leukemia, requiring drug discontinuation for resolution. 1 This represents a first-reported incidence of this complication with this second-generation BTK inhibitor, previously only described with first-generation agents. 1

Key Clinical Features of Zanubrutinib-Associated Pleural Effusion

• Onset timing: Pleural effusion can develop approximately 2 months after initiating zanubrutinib therapy 1
• Presentation: Patients present with worsening dyspnea secondary to hemorrhagic pleural effusion 1
• Recurrence pattern: Episodes can recur while continuing the medication 1
• Resolution: Discontinuation of zanubrutinib leads to symptom resolution and prevents further episodes 1

Management Algorithm for Pleural Effusion in Patients on Zanubrutinib

Step 1: Immediate Assessment and Drug Discontinuation

• Stop zanubrutinib immediately upon diagnosis of pleural effusion, as the drug is causative rather than therapeutic 1
• Perform thoracentesis for new and unexplained pleural effusions to confirm diagnosis and provide symptomatic relief 2
• Obtain pleural fluid analysis including cell count, chemistry, and cytology to distinguish hemorrhagic effusion from other etiologies 2, 3

Step 2: Symptomatic Management

• Drain large effusions to provide symptomatic relief regardless of etiology 2
• Limit initial drainage to 1-1.5 liters to avoid re-expansion pulmonary edema 4
• Consider small bore (10-14F) intercostal catheters for drainage if needed 4

Step 3: Alternative Treatment Considerations

• Do not restart zanubrutinib after hemorrhagic pleural effusion develops, as recurrence is expected 1
• Consider alternative BTK inhibitors or treatment regimens for the underlying hematologic malignancy in consultation with hematology/oncology 1
• Monitor for resolution of effusion after drug discontinuation 1

Important Clinical Distinctions

Zanubrutinib vs. Dasatinib-Related Pleural Effusions

While dasatinib (another tyrosine kinase inhibitor) causes pleural effusions in 28-33% of patients that may respond to steroids and diuretics 5, 6, zanubrutinib-associated effusions are hemorrhagic and require drug discontinuation rather than medical management. 1 This is a critical distinction that prevents inappropriate continuation of a causative agent.

Risk Factors for Bleeding Complications

• Concurrent anticoagulation therapy (such as apixaban) significantly increases bleeding risk with zanubrutinib 1
• Zanubrutinib is associated with major and minor bleeding events including intracranial hemorrhage, GI bleeding, and hematuria 1
• The hemorrhagic nature of the pleural effusion reflects the drug's systemic bleeding propensity 1

Common Pitfalls to Avoid

• Never continue zanubrutinib after hemorrhagic pleural effusion develops, as this leads to recurrent episodes 1
• Do not mistake zanubrutinib-induced hemorrhagic effusion for malignant pleural effusion from the underlying lymphoma, which would have different management implications 7, 3
• Avoid assuming all BTK inhibitors have the same pleural complications—zanubrutinib causes hemorrhagic effusion while dasatinib causes non-hemorrhagic effusion 5, 1
• Do not attempt pleurodesis for zanubrutinib-related effusion, as drug discontinuation is the definitive treatment 1