Calquence (acalabrutinib)

P1/2, N=49, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Apr 2026 --> Nov 2025

This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD-guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791.

P2, N=132, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2030 --> Mar 2031 | Trial primary completion date: May 2026 --> May 2027

P2, N=60, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=105, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2023 --> Sep 2028

These findings inform the long-term comparative efficacy of Bruton tyrosine kinase inhibitors and suggest that zanubrutinib may confer sustained PFS and OS benefits compared with ibrutinib and acalabrutinib in similar treatment-naive CLL populations. Graphical abstract and video available for this article. Overview of the Comparative Efficacy of Covalent BTK Inhibitors in Treatment-Naïve CLL/SLL With Six-Year Follow-Up (MP4 345006 kb).

Chronic lymphocytic leukaemia (CLL) most commonly transforms into aggressive lymphoma; development of chronic myeloid leukaemia (CML) in a patient with CLL should prompt evaluation for an independent myeloid clone rather than presumed transformation.Myeloid neoplasms in patients with CLL may arise from therapy-related leukemogenesis or divergent evolution from a shared hematopoietic progenitor, highlighting the importance of molecular characterization.Management of coexisting CLL and CML requires individualized risk-benefit assessment, particularly in elderly patients with prior solid tumours and immune dysfunction.

P3, N=42, Not yet recruiting, The First Affiliated Hospital of Soochow University

In real-world practice, venetoclax plus obinutuzumab was associated with longer TTNT and improved OS compared to acalabrutinib as first-line therapy in patients with TP53 wild-type CLL.

P2, N=108, Active, not recruiting, AstraZeneca | Trial primary completion date: Jul 2028 --> Oct 2028 | Trial completion date: Jul 2028 --> Oct 2028

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.

To date, neither randomized nor retrospective trials have directly compared these approaches in RR CLL, and only limited data are available comparing venetoclax plus obinutuzumab (VenObi) to BTKi in the first-line setting. We retrospectively analysed 352 patients receiving second-line therapy: 93 VenR and 259 BTKi (ibrutinib: n = 222; acalabrutinib: n = 37)...Treatment discontinuation due to adverse events before month 24 was more frequent with BTKi (22.5% with VenR vs. 34.3% with BTKi), primarily due to infections (10.6% vs. 28.6%) and disease progression (14.3% vs. 22.5%). These preliminary data suggest comparable outcomes and manageable toxicity profiles for both regimens.