First-line zanubrutinib versus bendamustine-rituximab for CLL/SLL: median five-year follow-up of phase 3 SEQUOIA trial

The multinational phase 3 SEQUOIA trial compares the oral BTK inhibitor zanubrutinb versus the combination bendamustine plus rituximab (BR) as first-line treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without del(17)(p13.1). Results of the trial with median 61.2 months of follow-up have now been published. Median progression-free survival was not reached in the zanubrutinib group versus 44.1 months in the BR group (HR 0.29; one-sided p=0.0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobuline heavy-chain variable region (IGHV) genes (HR 0.40; one-sided p=0.0003) and unmutated IGHV genes (HR 0.21; one-sided p<0.0001). Median overall survival was not reached in either group; estimated 60-months OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were observed. The authors conclude that at a median follow-up of 61.2 months, the results of SEQUOIA support zanubrutinib as a favorable first-line treatment for CLL/SLL.