Clinical trials with targeted therapies in CLL

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The study authors demonstrated in this first head-to-head trial of BTK inhibitors in patients with previously treated CLL, an acalabrutinib non-inferior progression-free survival with less cardiotoxicity and fewer discontinuations due to adverse events compared with ibrutinib.

The study authors conclude that the four-year follow-up confirms the superior efficacy with longer progression-free survival and deep remissions after fixed-duration venetoclax plus obinutuzumab (Ven-Obi) compared to chlorambucil-obinutuzumab (Clb-Obi). The majority of patients remain without relapse three years after completing Ven-Obi treatment. Although adverse features such as TP53 mutation/deletion were not fully mitigated, fixed-duration Ven-Obi continues to be an effective treatment for all patients with CLL and with coexisting conditions.


The study authors conclude that first-line ibrutinib plus venetoclax (Ibr + Ven) is an all-oral, once-daily, chemotherapy-free fixed-duration regimen that provides deep, durable responses in patients with CLL/SLL. Overall, CR, undetectable MRD rates, progression-free, and overall survival appear favorable, and the benefit was observed regardless of genomic high-risk features. No new safety signals were identified, and the safety profile of Ibr + Ven was consistent with the known safety profiles of each agent.


The study authors conclude that with a median follow-up of 46.9 months (~4 years) in the ELEVATE-TN study, the efficacy and safety of Acalabrutinib plus Obinutuzumab (A+O) and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.

The study authors confirm in this phase 2 study that treatment with obinutuzumab plus venetoclax (O-V) is well tolerated in FCR-unfit patients and both fixed duration V and MRD-guided V consolidation resulted in > 50% of patients with undetectable MRD and without progression after a maximum of 24 cycles of V, which warrants further study of MRD-guided or fixed consolidation treatment after O-V induction.