At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Jennifer R Brown, MD, PhD, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts, presented extended follow-up data from the ALPINE randomized phase 3 study.

At a median follow-up of 3 years, the study found that zanubrutinib treatment continued to demonstrate sustained progression-free survival (PFS) benefit over ibrutinib treatment for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Brown and colleagues noted that the study demonstrated that zanubrutinib continues to be an overall more efficacious and better-tolerated treatment than ibrutinib for patients with R/R CLL/SLL. 

Transcript: 

Hello, I'm Jennifer Brown. I'm director of the CLL Center and Institute physician at Dana Farber Cancer Institute and the Worthington and Margaret Colette professor of medicine in the field of hematologic oncology at Harvard Medical School. I'm here at the ASH annual meeting 2023, and I had the opportunity to present the ALPINE data. ALPINE is a phase 3 randomized trial comparing zanubrutinib to ibrutinib in relapsed/refractory CLL patients.

We had previously presented data last year at a 2-year follow-up: Does zanubrutinib improve both response rate and progression-free survival compared to ibrutinib? At this year's meeting, we have the opportunity to present a 39-month follow-up of the study. 

The patients have had a median of 1 prior regimen on each arm, and the arms were pretty well balanced. With this year's follow-up, we do see that the progression-free survival continues to be improved with zanubrutinib compared to ibrutinib, with 65% of patients in remission with zanubrutinib compared to 55% with ibrutinib.

The effect is even greater in our highest-risk population, in the 17p deleted population where we see that 59% of patients remain progression-free, with zanubrutinib compared to 41% with ibrutinib. 

The safety looks pretty similar and is generally balanced in terms of infections, neutropenia, and hypertension. But, cardiac safety is significantly better with zanubrutinib compared to ibrutinib, with fewer cardiac adverse events, fewer cardiac serious adverse events, fewer discontinuations due to cardiac causes, and fewer hospitalizations due to cardiac causes. Importantly, also, there were no cardiac deaths with zanubrutinib, whereas there [were] 6 with ibrutinib, or 1.9%. So, this is actually the first head-to-head study of 2 [Bruton's tyrosine kinase] (BTK) inhibitors to show efficacy superiority, and we believe, based on that, that zanubrutinib is an excellent choice for CLL therapy in relapsed patients.

Source: 

Brown JR, Eichhorst BF, Lamanna N, et al. Extended Follow-up of ALPINE Randomized Phase 3 Study Confirms Sustained Superior Progression-Free Survival of Zanubrutinib Versus Ibrutinib for Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (R/R CLL/SLL). Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 202