Zanubrutinib More Effective Than Ibrutinib in Treating Patients With Relapsed/Refractory CLL, SLL

Zanubrutinib maintained long-term improved safety and tolerability profiles over a roughly 3.5 year period in patients with relapsed/refractory 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 to ibrutinib—the first efficacy benefit seen in a head to head study of BTK [Bruton tyrosine kinase] inhibitors in CLL. The efficacy benefit is particularly notable among our highest risk subgroup, patients with 17p deletion. These results establish zanubrutinib as a therapy of choice for our CLL patients,” coauthor Jennifer Brown, MD, PhD, of Dana-Farber Cancer Institute, told The American Journal of Managed Care^®.

Progression-free survival by the end of the trial remained elevated with zanubrutinib vs ibrutinib, including in patients with del(17p)/TP53 mutation| 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 underwent treatment 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 an earlier finding that evaluated the same patient cohort and concluded that zanubrutinib outperformed ibrutinib.

Progression-free survival (PFS) by the end of the trial remained elevated with zanubrutinib vs ibrutinib (HR, 0.68; 95% CI, 0.54-0.84), including in patients with del(17p)/TP53 mutation (HR, 0.51; 95% CI, 0.33-0.78). Overall response rate at trial 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).

Fewer than a quarter of patients who received zanubrutinib discontinued treatment because of adverse events (AEs), while the same was true for more than a quarter of patients receiving ibrutinib (21.4% vs 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 following AEs occurred in 59.3% vs 62% and 14.8% vs 18.2% of patients with zanubrutinib vs ibrutinib, respectively. Zanubrutinib led to fewer AEs that required 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 AEs included COVID-19–related infection (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. Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%). No cardiac deaths were reported with zanubrutinib vs six cardiac deaths with ibrutinib.

Zanubrutinib is an antineoplastic agent that prevents cancer cells from growing, 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 head-to-head study of covalent or non-covalent BTKis to show superior efficacy. Now, with median study follow-up of 42.5 months, zanubrutinib has been shown to offer a sustained PFS benefit vs ibrutinib, with a 32% reduction in risk of progression or death,” the authors wrote. “The PFS benefits with zanubrutinib continue to extend to the predefined high-risk del(17p)/TP53mut population, where risk of progression or death was 49% lower with zanubrutinib than with ibrutinib. This differs from an analysis after a similar median follow-up from the ELEVATE-RR study comparing acalabrutinib to ibrutinib, where patients with previously treated CLL with del(17p) or del(11) showed no difference in the risk of progression or death, suggesting a clear differentiation of zanubrutinib among BTKi in this disease.”

References

1. Brown J, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. 2024. Blood. doi: 10.1182/blood.2024024667
2. Zanubrutinib. Mayo Clinic. Accessed Oct. 1, 2024. https://www.mayoclinic.org/drugs-supplements/zanubrutinib-oral-route/description/drg-20477009