biostudies-literatureUnknown15(5)Frustaci AMIbrutinib revolutionized the CLL treatment approach and prognosis demonstrating its efficacy and safety even at extended follow-up. During the last few years, several next-generation inhibitors have been developed to overcome the occurrence of toxicity or resistance in patients on continuous treatment. In a head-to-head comparison of two phase III trials, both acalabrutinib and zanubrutinib demonstrated a lower incidence of adverse events in respect to ibrutinib. Nevertheless, resistance mutations remain a concern with continuous therapy and were demonstrated with both first- and next-generation covalent inhibitors. Reversible inhibitors showed efficacy independently of previous treatment and the presence of BTK mutations. Other strategies are currently under development in CLL, especiallyCancers1504https://www.ebi.ac.uk/biostudies/studies/S-EPMC10000925biostudies-literatureNext Generation BTK Inhibitors in CLL: Evolving Challenges and New Opportunities.PMC10000925Tedeschi AMontillo MCairoli RFrustaci AMDeodato MZamprogna GfalseNext Generation BTK Inhibitors in CLL: Evolving Challenges and New Opportunities.Ibrutinib revolutionized the CLL treatment approach and prognosis demonstrating its efficacy and safety even at extended follow-up. During the last few years, several next-generation inhibitors have been developed to overcome the occurrence of toxicity or resistance in patients on continuous treatment. In a head-to-head comparison of two phase III trials, both acalabrutinib and zanubrutinib demonstrated a lower incidence of adverse events in respect to ibrutinib. Nevertheless, resistance mutations remain a concern with continuous therapy and were demonstrated with both first- and next-generation covalent inhibitors. Reversible inhibitors showed efficacy independently of previous treatment and the presence of BTK mutations. Other strategies are currently under development in CLL, especially2023-01-01T00:00:00Z2023 Feb2025-04-04T03:41:42.59Z2025-04-04T03:41:42.59ZS-EPMC100009253690029510.3390/cancers15051504