Brukinsa (zanubrutinib)

P3, N=122, Active, not recruiting, International Extranodal Lymphoma Study Group (IELSG) | Recruiting --> Active, not recruiting

P2, N=40, Not yet recruiting, Canadian Cancer Trials Group

The primary first-line treatment options for CLL comprise continuous therapies based on the BTK inhibitors ibrutinib, zanubrutinib, or acalabrutinib, or fixed-duration regimens combining the BCL2 inhibitor venetoclax with obinutuzumab or the BTK inhibitors ibrutinib or acalabrutinib (with or without obinutuzumab). Selecting the appropriate targeted therapy requires careful evaluation of a multitude of factors, including molecular disease features (especially del[17p]/TP53 and IGHV mutational status), comorbidities, comedications, and the patient's preferences. Focusing on primary treatment options, we review data from the key controlled trials that support the first-line use of targeted therapies for patients with CLL, consider ongoing trials that may support clinical decision-making in the future, and assess the potential to personalize treatment regimens in CLL based on minimal residual disease status.

We report a case of a 63-year-old male with a history of CLL previously treated with ibrutinib but discontinued early due to intolerance. As a result, the patient was then treated with obinutuzumab plus venetoclax, achieving undetectable minimal residual disease (MRD) but relapsed after 2 years with CNS involvement...He remains in complete remission with continued daily zanubrutinib 6 months follow-up; no significant adverse effects were observed. This case highlights the rare occurrence of CNS involvement in CLL and is the first to demonstrate successful CNS disease eradication with zanubrutinib monotherapy.

P3, N=466, Not yet recruiting, Alliance for Clinical Trials in Oncology

These findings provide real-world evidence that zanubrutinib offers more durable disease control and improved persistence compared with ibrutinib, reinforcing its clinical value as a preferred second-generation BTKi. Nevertheless, the relatively short follow-up for zanubrutinib warrants cautious interpretation of long-term outcomes and underscores the need for ongoing observation to fully characterize its durability and safety.

P=N/A, N=212, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Recruiting --> Active, not recruiting | N=125 --> 212

The cBTKi + V regimen is easy to manage and relatively well tolerated. However, cBTKi-related cardiovascular toxicities remain a limiting concern, especially for the use of cBTKi + V in some older patients.

P1, N=60, Not yet recruiting, Peking University People's Hospital

P2, N=34, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P=N/A, N=50, Not yet recruiting, Zhengzhou University

P3, N=300, Recruiting, BeOne Medicines | Trial completion date: Oct 2032 --> Mar 2032 | Trial primary completion date: Mar 2029 --> Aug 2028