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

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

Progression-free survival at the end of the trial remained high with zanubrutinib compared to ibrutinib, including in patients with a del(17p)/TP53| Image credit: © Amazing Studio – stock.adobe.com

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

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

Less than a quarter of patients receiving zanubbrutinib discontinued treatment due to adverse events (AEs), compared with more than a quarter of patients receiving ibrutinib (21.4 % versus 28.3%). Similarly, zanubrutinib outperformed ibrutinib in treatment discontinuation due to disease progression (18% vs. 22.5%). Dose interruption and reduction following AEs occurred in 59.3% versus 62% and 14.8% versus 18.2% of patients receiving zanubrutinib versus ibrutinib, respectively. Zanubrutinib resulted in fewer AEs requiring hospitalization than 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 non-hematologic AEs included COVID-19 infections (46% vs. 33.3%), diarrhea (18.8% vs. 25.6%), upper respiratory tract infections (29.3% versus 19.8%) and hypertension (27.2% versus 25.3%). . Cardiac events were lower with zanubbrutinib (25.9% vs. 35.5%) despite similar rates of hypertension. The incidence of atrial fibrillation/flutter was lower with zanubrutinib than with ibrutinib (7.1% vs. 17.0%). No cardiac deaths were reported with zanubrutinib compared to six cardiac deaths with ibrutinib.

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

BTK is a main component of the B-cell receptor signaling pathway in B-cell malignancies, according to the study. 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 comparative study on covalent or non-covalent BTK to show superior effectiveness. Now, with a median study follow-up of 42.5 months, zanubbrutinib has been shown to provide sustained PFS benefit compared to ibrutinib, with a 32% reduction in progression risk. or death,” the authors wrote. “The PFS benefits of zanubbrutinib continue to extend to the predefined high-risk del(17p)/TP53mut population, where the risk of progression or death was 49% lower with zanubbrutinib than with ibrutinib. This differs from an analysis performed after similar median follow-up in the ELEVATE-RR study comparing acalabrutinib versus ibrutinib, in which CLL patients previously treated with del(17p) or del(11) did not showed no difference in the risk of progression or death, suggesting a clear differentiation of zanubbrutinib among BTKi in this disease.

References

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