Dr. Rhee on the Benefit of Zanubrutinib Vs Ibrutinib in R/R CLL

June-Wha Rhee, MD, cardiologist, assistant professor, Division of Cardiology, Department of Medicine, City of Hope, discusses the benefit of zanubrutinib (Brukinsa) vs ibrutinib (Imbruvica) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), as well as the incidence of cardiac disorders associated with the BTK inhibitors.

In the phase 3 ALPINE trial (NCT03734016), 652 patients with relapsed/refractory CLL were randomly assigned to receive zanubrutinib at 160 mg twice per day or ibrutinib at 420 mg once per day. In the final analysis of the multi-national, randomized, controlled trial, it was found at a median follow-up of 29.4 months that zanubrutinib elicited a superior progression-free survival compared with ibrutinib (HR, 0.65; 95% CI, 0.49-0.86; P = .002). Additionally, zanubrutinib demonstrated a lower incidence of cardiac adverse effects (AEs). 

Previous data in patients with relapsed/refractory CLL showed that treatment with was associated with increased risk of cardiovascular complications, leading to the discontinuation of treatment, as well as potentially worse oncologic and cardiovascular outcomes, Rhee says.

In APLPINE, it was found that the incidence of atrial fibrillation was much lower in patients treated with zanubrutinib vs patients treated with ibrutinib, Rhee continues. In patients treated with zanubrutinib, 5.2% experienced any-grade atrial fibrillation, compared with 13.3% in the ibrutinib group. Additionally, 1 patient in the zanubrutinib group had to discontinue treatment due to cardiac complications vs 14 patients in the ibrutinib group. Additionally, 6 deaths due to cardiac events were reported, and all occurred in patients who received ibrutinib.

Overall, it appears that the patients who were treated with zanubrutinib were also able to tolerate treatment better without needing to discontinue due to cardiovascular risk, Rhee says. Given the cardiovascular complications associated with ibrutinib, these data for zanubrutinib are encouraging and reassuring data for cardiologists, oncologists, and patients, Rhee concludes.