Thirty-one of 59 (53%) R/R pts carried at least 1 hotspot BTK mutation (p.C481S/R/Y) (median VAF 23.3%, range, 1.4%>97.3%) (Table 1). Eight of 31 (26%) mutated pts carried ≥2 hotspot BTK mutations with different VAFs. Seven R/R pts harboring BTK mutation(s) also carried PLCG2 mutation(s) (Table 1). This study reveals that ~50% of pts relapsing on ibrutinib had a BTK p.C481 mutation by NGS.