BTK and B-cell chronic lymphocytic leukemia: For example, mutationof Cys797 of EGFR is a major resistance mechanism to osimertinib,a covalent inhibitor that is currently prescribed as first-line therapyfor mutant EGFR-dependent non-small cell lung cancer (NSCLC).8,9 Likewise, Cys481 mutation is a common resistance mechanism to thecovalent BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL).9 A similar mechanism of resistance has also beendocumented for the recently approved covalent inhibitors of KRASG12C.