In the randomized ALPINE trial, #Zanubrutinib (second-generation BTK inhibitor) improved the outcomes versus #ibrutinib (first-generation BTK inhibitor) in patients with relapsed/ resistant CLL & SLL with better cardiac safety profile.

In this phase III study, 652 patients with relapsed/refractory chronic lymphocytic leukemia were randomized to receive zanubrutinib or ibrutinib. Interim analysis after 15 months of median follow-up, the overall response rate (ORR) (partial or complete response) was significantly higher with zanubrutinib (78.3%) versus ibrutinib (62.5%) (P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%). In the final analysis after 29.6 months of follow-up, the progression-free survival at 24 months were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. PFS was also higher in patients with del(17p)/TP53 mutations (HR = 0.53; 95% CI, 0.31 to 0.88).