Indeed, ibrutinib and other BTKis, but also the spleen tyrosine kinase (SYK) inhibitor fostamatinib and the phosphoinositide 3′-kinase (PI3K) isoform p110δ (PI3Kδ) inhibitor idelalisib, have similar clinical manifestations consisting in a rapid resolution of lymphadenopathy and a redistribution of CLL cells from the tissues into the circulation accompanied by a transient lymphocytosis [190,191,192]. Here, PIK3CD is linked to B-cell chronic lymphocytic leukemia.