Safe and effective rechallenge of zanubrutinib in combination with obinutumumab in follicular lymphoma after severe drug-induced liver injury

Introduction Severe liver injury is uncommonly encountered in zanubrutinib and other bruton tyrosine kinase inhibitors. In previous reports of severe liver toxicity associated with bruton kinase inhibitors, the offending agents were often withdrawn although resumption of ibrutinib was ever reported. Case Report We shared our clinical experience of 2 cases of follicular lymphoma treated with obinutumumab and zanubrutinib. Severe liver injury, as shown by high levels of transaminase (ALT up to 1350 and 406 IU/L respectively) occurred within a week of drug exposure. Management and Outcome Zanubrutinib was withdrawn shortly then resumed with low dose (80 mg) after hepatic enzyme levels stablized. The dose was titrated up to full dose (320 mg) and lymphoma responded well (partial response in one and complete response in the other) to treatment. Conclusion This report highlighted a rare but important complication of zanubrutinib. On the other hand, it also suggests zanubrutinb should not be excluded from subsequent treatment and can be re-introduced with caution.