There have been reports of resistance to ibrutinib. Recent reports have shown that a mutation that changed the cysteine at BTK position 481 to serine (C481S) is one of the mechanisms responsible for resistance blocking the ability of ibrutinib to bind covalently to BTK. Another mechanism involved in acquiring resistant to this agent is a gain-of-function mutations found in PLCγ2, a downstream target of the BTK phosphorylation pathway