BTK and B-cell chronic lymphocytic leukemia: For patients with covalent BTK inhibitor-resistant CLL, current clinical guidelines (e.g., ESMO and NCCN) recommend venetoclax-based regimens, typically combined with anti-CD20 monoclonal antibodies such as rituximab or obinutuzumab, and non-covalent BTK inhibitors like pirtobrutinib, which have shown efficacy in overcoming resistance [5, 6].