Auranofin (AF) can induce oxidative stress and apoptosis in CLL cells in vitro.

Phase II study investigated in vivo effect of AF on patients with relapsed/refractory CLL and one patient with Small Lymphocytic Lymphoma SLL.

initial dose 6 mg daily administered orally on 28-day cycles, with dose escalation to 9 mg after first cycle if no grade ≥2 toxicity occurred.

After 24 hours of therapy, AF induced a significant decrease in expression of NRF2 signature in CLL cell and that these changes resolved by D7.

AF decrease anti-oxidant defenses regulated by NRF2 concomitant with increase in cellular ROS levels and induction of some degree of cellular apoptosis.

AF can increase ROS production and apoptosis but effect transient and completely resolved by D7 consistent with limited clinical activity observed in study.