Multinational phase 3 study of zanubrutinib versus ibrutinib for relapsed or refractory CLL/SLL

The first-generation BTK inhibitor ibrutinib is standard therapy for CLL/SLL, but off-target effects can limit its use. The multinational phase 3 ALPINE trial randomized patients with relapsed or refractory (R/R) CLL/SLL to ibrutinib or the next-generation BTK inhitibor zanubrutinib. With a median follow-up of 29.6 months the PFS was significantly prolonged in the zanubritinib arm compared to the ibrutinib arm, both in the ITT population and in the del(17p)/TP53 mutated population. Zanubrutinib had a favorable safety profile compared with ibrutinib. There were no grade 5 cardiac AEs in the zanubrutinib arm compared with 1.9% of patients in the ibrutinib arm. Treatment discontinuation was lower with zanubrutinib (26.3%) versus ibrutinib (41.2%). The authors conclude that zanubrutinib is more efficacious and better tolerated than ibrutinib as treatment for R/R CLL/SLL.