Drug resistance is a common problem during cancer treatment as it limits the effectiveness of the therapy. The resistance can arise before or during treatment. 31 Recent studies report the development of acquired resistance to both ibrutinib and acalabrutinib in a sub-population of patients with CLL and mantle cell lymphoma. 26 , 32 , 33 , 34 Until now, point mutations causing single amino acid replacement in BTK as well as acquired activating variations in PLC?2 have been reported.
