Alexey Danilov, MD, PhD, Co-Director, Toni Stephenson Lymphoma Center and Professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, California, commented on the phase III ALPINE trial comparing ibrutinib and zanubrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). “The study found a significant improvement in progression-free survival with zanubrutinib,” Dr. Danilov said. “This benefit was also seen among patients with CLL who had aberrant TP53, a difficult-to-treat population.”

Alexey Danilov, MD, PhD

Dr. Danilov continued: “Consistent with previous reports from this study, zanubrutinib was associated with a more favorable adverse-event profile compared with ibrutinib, including lower rates of atrial fibrillation. There are a few potential caveats to consider, such as a a relatively high drug discontinuation rate for both zanubrutinib and ibrutinib. However, the ibrutinib discontinuation rate in this study is similar in frequency to that seen in real-world analyses, and thus, this current study may, in fact, be more reflective of everyday practice. Although one might also note that the ibrutinib arm was associated with somewhat inferior efficacy compared with earlier trials of ibrutinib in relapsed or refractory CLL, such as RESONATE, cross-trial comparisons are rarely reliable, and the experimental (zanubrutinib) and control (ibrutinib) cohorts were well balanced in this study. Thus, the improved efficacy data and the overall better tolerability of zanubrutinib in patients with CLL/SLL position it, along with another selective BTK inhibitor, acalabrutinib, as a preferred therapeutic option for patients with CLL. Zanubrutinib is now incorporated in the NCCN Compendium.” n

DISCLOSURE: Dr. Danilov has served as a consultant to AstraZeneca, AbbVie, BeiGene, Genentech, Nurix, MorphoSys, Incyte, TG Therapeutics, Bayer Oncology, and Pharmacyclics; and has received research funding from AstraZeneca, Takeda Oncology, Bayer Oncology, SecuraBio, MEI Pharma, Nurix, Cyclacel, TG Therapeutics, and Bristol Myers Squibb.