Brukinsa (zanubrutinib)

P2, N=76, Recruiting, University Health Network, Toronto | Trial completion date: Dec 2027 --> Dec 2029 | Trial primary completion date: Apr 2026 --> Apr 2029

P1/2, N=258, Recruiting, BeOne Medicines | N=56 --> 258 | Trial completion date: Dec 2027 --> Nov 2032 | Active, not recruiting --> Recruiting | Trial primary completion date: Jun 2027 --> Nov 2029

This case highlights the diagnostic complexity of composite indolent B-cell lymphomas and underscores the importance of integrated clinical, morphologic, immunophenotypic, and molecular assessment to inform management and surveillance.

Second, a network meta-analysis ranked the efficacy and safety of regimens including rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R); R-CHOP plus lenalidomide (R2-CHOP); R-CHOP plus ibrutinib (I+R-CHOP); R-CHOP plus zanubrutinib (Z+R-CHOP); and R-CHOP plus venetoclax (Ven-R-CHOP). DEL is a distinct high-risk subtype with quantifiable prognostic detriment. Z+R-CHOP emerges as a promising strategy requiring validation in prospective studies.

Bruton tyrosine kinase inhibidors (BTKI), such as ibrutinib and zanubrutinib, represent a cornerstone of CLL/SLL treatment by inhibiting B-cell receptor signaling. The patient improved after BTKI reintroduction, and a P-RT was diagnosed. Nine similar patients were found through PubMed search, and we describe their clinicopathological characteristics.

P2, N=35, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P2, N=178, Not yet recruiting, Ruijin Hospital

P2, N=41, Recruiting, Huazhong University of Science and Technology | Trial primary completion date: Dec 2025 --> Jul 2026

P3, N=510, Active, not recruiting, BeOne Medicines | Trial completion date: Dec 2027 --> Sep 2031

Previous studies have shown that the combination of the second-generation BTKi zanubrutinib and polatuzumab vedotin, within the R-CHOP regimen, yielded higher response rates in preliminary clinical studies; however, the efficacy of this combination remains unclear. Notably, the combination showed superior synergistic efficacy in GCB-subtype cells. In conclusion, these findings provide a novel mechanistic rationale for combining zanubrutinib and polatuzumab vedotin in DLBCL treatment, regardless of cell-of-origin subtype.

In this review, we consider the pharmacologic properties of zanubrutinib that differentiate it from ibrutinib and acalabrutinib, and provide a comprehensive overview of the efficacy and safety data that led to zanubrutinib monotherapy becoming a preferred therapy for a significant subgroup of patients with CLL/SLL. We also highlight trials in CLL/SLL and Richter's transformation with zanubrutinib in targeted therapy combinations that offer the potential for time-limited treatment courses.

P2, N=40, Recruiting, Canadian Cancer Trials Group | Initiation date: Mar 2026 --> Jun 2026 | Not yet recruiting --> Recruiting