Dr Peter Hillmen Discusses the Interim Results of the Phase 3 ALPINE Study of Zanubrutinib vs Ibrutinib

The interim results on the first 415 patients randomized in the phase 3 ALPINE study showed a significantly better response for zanubrutinib compared with ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic leukemia, said Peter Hillmen, PhD, MB ChB, professor at the University of Leeds and honorary consultant hematologist at Leeds Teaching Hospitals NHS Trust.

What do the interim results of the phase 3 ALPINE study of zanubritinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic leukemia show so far?

The ALPINE study compared zanubrutinib with ibrutinib, which are second-generation Bruton tyrosine kinase (BTK) inhibitors. The study is a large trial with 652 patients, but the interim results being presented at the European Hematology Association meeting are of the first 415 patients who were randomized.

The primary end point was overall response rate, which allowed for the trial to be reported earlier, and the follow-up is relatively short. The overall response was significantly better for zanubrutinib compared with ibrutinib at the 12-month time point, Hillmen explained. The outcome of the progression-free survival was also in favor of zanubrutinib, he added.

“As yet, not a significant difference in overall survival, although there is a trend to watch that space,” Hillmen said. “Also there’s a reduction, a significant reduction, in atrial fibrillation from 10% to 2.5% for zanu[brutinib].”

The study will be followed longer, the numbers will change, and there will be new adverse effects.

“There’s been a difference in hypertension, which is interesting, but that might be to do with the short follow-up,” Hillmen said. “So, I think we need further follow-up for the ALPINE study.”