Infectious toxicity in patients with CLL treated with the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib is most common in the first 6 months of therapy and is caused by on-target and off-target effects of this BTKi on NKs, CD4+ macrophages, CD8+ macrophages, Tregs and cytotoxic T lymphocytes (Figure 1). Here, BTK is linked to B-cell chronic lymphocytic leukemia.