Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma

Bruton tyrosine kinase (BTK) inhibitors are approved in several B-cell malignancies, including the recent authorization of zanubrutinib for relapsed or refractory follicular lymphoma (FL).

Based on preclinical studies demonstrating synergy with ibrutinib and the B-cell lymphoma (BCL)-2 inhibitor, venetoclax, in FL cell lines, we conducted a multicenter phase Ib/II study evaluating this combination in relapsed or refractory FL.

The recommended phase 2 dose was ibrutinib 560 mg and venetoclax 600 mg. There was no evidence of clinical tumor lysis syndrome, despite the omission of a venetoclax ramp up. At a median duration of therapy of 6 months, the most common adverse events were low grade diarrhea (83%), infection (75%), and rash (58%). Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median progression-free survival was 8.2 months, and the median duration of CR (n = 5) was 38 months.

The combination of a BTK and BCL2 inhibitor is efficacious in relapsed/refractory FL and represents a unique dual-targeted approach warranting further investigation.