Multicenter phase 1 trial of zandelisib plus zanubrutinib for previously treated follicular and mantle cell lymphomas

Among patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL), the combination of the PI3Kδ inhibitor zandelisib and the BTK inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. A multicenter phase 1 trial in the United States evaluated the combination for previously treated FL and MCL. The combination was tolerated, with 3 of 50 patients discontinuing due to adverse events. The overall response rate was 87% (33% complete response) in the FL group and 74% (47 CR) in the MCL group. The median duration of response was not reached during 16.5 months of follow-up in de FL group and 10.9 months in the MCL group. The estimated 1-year progression-free survival was 72.3% (95% CI 51.9-85.1) in the FL group and 56.3% (28.9-76.6) in the MCL group. The authors conclude that the combination of zandelisib and zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone (visual abstract).