Imbruvica (ibrutinib)

Altogether, these findings suggest administering ibrutinib before leukapheresis may modify T-cell characteristics in the collected material, thereby improving final CAR T-cell product quality and clinical outcomes for patients with R/R LBLC treated with tisagenlecleucel. This trial was registered at www.clinicaltrials.gov as #NCT03876028.

P2, N=129, Active, not recruiting, Canadian Cancer Trials Group | Trial primary completion date: Dec 2025 --> Mar 2026

To characterize CH in CLL, 620 patients from two German CLL Study Group trials were analyzed (CLL12 (ibrutinib vs. placebo) and CLL14 (venetoclax-obinutuzumab [Ven-Obi] vs. chlorambucil-obinutuzumab [Clb-Obi])) using error-corrected next-generation sequencing with a VAF threshold of 0.5%. In contrast, CH had no prognostic impact in patients receiving targeted therapies. This study demonstrates the high prevalence of CH, highlights its differential impact across various CLL therapies and underscores its adverse influence on patient outcomes.

Overall, FTO promotes DLBCL progression and ibrutinib resistance by demethylating Myc mRNA and stabilizing its expression. These findings highlight the FTO-m6A-Myc axis as a potential therapeutic target for overcoming drug resistance in DLBCL.

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.

P2, N=60, Active, not recruiting, Acerta Pharma BV | Trial completion date: Sep 2026 --> Jun 2026

We compared an MRD-guided, fixed-duration ibrutinib-venetoclax (IV) regimen to fludarabine-cyclophosphamide-rituximab (FCR) in this population. A patient profile suitable for an MRD-guided, fixed-duration IV regimen requires consideration of potential toxicities. Abbvie and Janssen France.

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.

P2, N=42, Active, not recruiting, Jennifer Woyach | Trial completion date: Dec 2025 --> Dec 2026

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.

Future studies should explore long-term durability beyond 5 years and validate MRD thresholds for treatment cessation. National Nature Science Foundation of China, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Xisike Clinical Oncology Research Foundation.

P1, N=14, Completed, Alliance Foundation Trials, LLC. | Active, not recruiting --> Completed