Brukinsa (zanubrutinib)

The patient's condition stabilized following targeted therapy with zanubrutinib and rituximab (ZR regimen). This case underscores the complexity of diagnosing dual hematological anomalies, highlights the importance of multidisciplinary collaboration, and seeks to explore the potential pathophysiological link between LPL and spherocytosis, offering a reference for diagnosis and treatment in similar clinical scenarios.

P2, N=15, Recruiting, Baptist Health South Florida | Trial completion date: Feb 2031 --> Feb 2033 | Trial primary completion date: Feb 2026 --> Feb 2028

P2, N=50, Active, not recruiting, Weill Medical College of Cornell University | Recruiting --> Active, not recruiting

P3, N=500, Recruiting, BeOne Medicines | Not yet recruiting --> Recruiting

P2, N=94, Active, not recruiting, BeOne Medicines | Trial completion date: Jun 2030 --> Sep 2029 | Trial primary completion date: Oct 2027 --> Nov 2026

To this end, bridging therapy with Brutonyg tyrosine kinase inhibitors (BTKi), such as ibrutinib or zanubrutinib, is being investigated as a strategy to improve treatment outcomes. Further investigations are essential to validate and translate these observations into clinical practice, thus highlighting the need for further research in this area. https://www.chictr.org.cn/showproj.aspx?proj=33185, ChiCTR1800019622.

P2, N=33, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P1/2, N=99, Recruiting, BeOne Medicines AG

P1/2, N=50, Not yet recruiting, Azienda Ospedaliera di Padova

P2, N=108, Recruiting, Curis, Inc. | Not yet recruiting --> Recruiting

P2, N=25, Completed, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Completed | N=55 --> 25

First-generation BTKi such as ibrutinib demonstrate antithrombotic efficacy but are limited by off-target effects, including bleeding and atrial fibrillation. Second- and third-generation inhibitors (eg, acalabrutinib, zanubrutinib, and pirtobrutinib) show enhanced selectivity, reducing cardiovascular toxicity in patients with B-cell malignancies. Highly selective BTKi (fenebrutinib and remibrutinib) do not show bleeding in clinical trials of various autoimmune disorders, and covalent selective BTKi applied at low dosage are expected to selectively inhibit Btk in platelets without bleeding side effects. Preclinical data and early observations from compassionate use in patients with atypical autoimmune thrombosis highlight the potential of BTKi as selective antithrombotic agents beyond traditional therapies. This review conceptualizes and underscores Btk's pivotal role at immune-thrombosis interfaces in atherothrombosis, advocating for precision medicine approaches and innovative platforms to unlock its full therapeutic potential in cardiovascular disease management.