Zanubrutinib maintained improved long-term safety and tolerability profiles over approximately 3.5 years in relapsed/refractory patients. chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma compared with ibrutinib, according to a randomized trial published in Blood.¹

“In this study we report that, with longer-term follow-up, zanubrutinib continues to show improved efficacy and toxicity compared with ibrutinib—the first efficacy benefit seen in a head-to-head trial of BTK (Bruton tyrosine kinase) inhibitors in LLC. The efficacy benefit is particularly notable among our highest-risk subgroup, patients with the 17p deletion. These results establish zanubrutinib as the therapy of choice for our CLL patients,” said co-author Jennifer Brown, MD, PhD, Dana-Farber Cancer Institute, The American Journal of Managed Care^®.

Progression-free survival to the end of the study remained increased with zanubrutinib versus ibrutinib, including patients with the del(17p)/TP53 mutation | Image credit: © amazing studio – stock.adobe.com

The study followed 652 patients from North America, Europe and Asia-Pacific for an average of 42.5 months. About half, or 327, received zanubrutinib, while 325 received ibrutinib. All patients were treated between November 2018 and December 2020. Median exposure time was 41.2 and 37.8 months in the zanubrutinib and ibrutinib arms, respectively. The study reports final comparison data for a previous finding that evaluated the same cohort of patients and concluded that zanubrutinib outperformed ibrutinib.

Progression-free survival (PFS) to the end of the study remained increased with zanubrutinib versus ibrutinib (HR, 0.68; 95% CI, 0.54-0.84), including patients with the del(17p)/TP53 mutation ( HR, 0.51; 95). %CI, 0.33-0.78). The overall response rate at study completion was higher with zanubrutinib compared with ibrutinib (85.6% vs. 75.4%). Complete response and complete response with incomplete bone marrow recovery rates were 11.6% (zanubrutinib) and 7.7% (ibrutinib).

Less than a quarter of patients receiving zanubrutinib discontinued treatment due to adverse events (AEs), while the same was true for more than a quarter of patients receiving ibrutinib (21.4% vs. of 28.3%). Zanubrutinib similarly outperformed ibrutinib when it came to stopping treatment due to disease progression (18% vs. 22.5%). Dose interruption and dose reduction due to adverse reactions occurred in 59.3% versus 62% and 14.8% versus 18.2% of patients on zanubrutinib versus ibrutinib, respectively. Zanubrutinib resulted in fewer adverse reactions requiring hospitalization compared with ibrutinib (48.5% vs. 57.1%).

Zanubrutinib was associated with fewer deaths than ibrutinib (HR, 0.77; 95% CI, 0.55-1.06). The most common nonhematologic adverse reactions included infection related to COVID-19 (46% 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%). . Cardiac events were lower with zanubrutinib (25.9% vs. 35.5%), despite similar rates of hypertension. The incidence of atrial fibrillation/flutter was lower with zanubrutinib versus ibrutinib (7.1% versus 17.0%). No cardiac deaths were reported with zanubrutinib compared with six cardiac deaths with ibrutinib.

Zanubrutinib is an antineoplastic agent that prevents the growth of cancer cells, according to the Mayo Clinic.²

According to the study, BTK is a major component of the B-cell receptor signaling pathway in B-cell malignancies. Ibrutinib was the first BTK inhibitor (BTKi) approved for the treatment of CLL. Zanubrutinib was developed for greater BTK specificity and increased potency.

“ALPINE is the only head-to-head study of covalent or non-covalent BTKis showing superior efficacy. Now, with a median study follow-up of 42.5 months, zanubrutinib has been shown to provide a sustained PFS benefit over ibrutinib, with a 32% reduction in the risk of progression or death,” the authors wrote. “PFS benefits with zanubrutinib continue to extend to the pre-defined high-risk del(17p)/TP53mut population, where the risk of progression or death was 49% lower with zanubrutinib than with ibrutinib. This differs from an analysis after a similar median follow-up in the ELEVATE-RR trial comparing acalabrutinib with ibrutinib, where CLL patients previously treated with del(17p) or del(11) showed no difference in risk of progression or death, suggesting clear differentiation of zanubrutinib between BTKi in this disease.”

reference

1. Brown J, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/CLL: ALPINE final comparative analysis. 2024. Blood. two: 10.1182/blood.2024024667
2. Zanubrutinib. Mayo Clinic. Accessed 1 October 2024.