According to the speaker, what is a common mechanism of resistance to covalent BTK inhibitors such as ibrutinib in CLL, and how can it be overcome?
A BTK C481S mutation that prevents covalent drug binding; the non-covalent inhibitor pirtobrutinib still binds BTK and remains effective, and BTK degraders offer a further option.
Loss of CD20 expression on CLL cells; switching to a different anti-CD20 antibody restores response to BTK inhibition.
A BCR::ABL1 fusion that bypasses BTK signaling entirely, so patients must abandon BTK-targeted therapy and switch to a PI3K or Syk inhibitor.