Figure 3.

Timeline and frequency of occurrence of resistance-associated mutations emergence in CLL patients who progressed on ibrutinib treatment. Resistance-associated mutations in BTK and PLCG2 genes usually develop between the second and fourth year of ibrutinib treatment. Mutated clones may occur at low allelic frequencies and may be detected several months before clinical relapse. Richter transformation is an early event that usually develops during the first 15 months of treatment with ibrutinib. Adapted from Ahn et al. (12).