ALPINE Final Analysis: Zanubrutinib Superior to Ibrutinib for Treatment of CLL, SLL

Compared to ibrutinib, zanubrutinib showed sustained benefit in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) in the final comparative analysis of the ALPINE trial.

The study was led by Jennifer R. Brown, MD, of the Dana-Farber Cancer Institute, and published in Blood.

A total of 652 patients were randomized to receive either zanubrutinib 160 mg twice daily (n=327) or ibrutinib 420 mg once daily (n=325). The primary endpoint was overall response rate (ORR), defined as the percentage of patients who achieved complete response or complete response with incomplete bone marrow recovery (CR/CRi), nodular partial response, or partial response. Secondary endpoints included progression-free survival (PFS), rate of atrial fibrillation or flutter, overall survival (OS), and safety.

The ORR was 85.6% for the zanubrutinib group, compared to 75.4% for the ibrutinib group. The CR/CRi rates were 11.6% for zanubrutinib and 7.7% for ibrutinib. The median OS was not reached in either group, and the 36-month PFS rate was 65.4% for zanubrutinib and 54.4% for ibrutinib. The PFS benefit for zanubrutinib was sustained over ibrutinib (HR: 0.68 [95% CI, 0.54-0.84]) with a median of 42.5 months follow-up.

The researchers noted that no new safety signals have been observed. For zanubrutinib and ibrutinib, respectively, the most common nonhematological events were COVID-19 related infection (46.0% vs 33.3%), diarrhea (18.8% vs 25.6%), upper respiratory tract infection (29.3% vs 19.8%), and hypertension (27.2% vs 25.3%). The zanubrutinib group, compared to the ibrutinib group, had lower incidence of cardiac events (25.9% vs 35.5%, respectively) and atrial fibrillation or flutter (7.1% vs 17.0%, respectively). No cardiac deaths were reported in the zanubrutinib group, while six cardiac deaths were reported in the ibrutinib group.

“This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety [and] tolerability profile,” the researchers wrote.

Reference

Brown JR, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024. doi:10.1182/blood.2024024667