Dr. Brown:
Hello. I'm Dr. Jennifer Brown, from Dana-Farber Cancer Institute, where I'm Director of the CLL Center, and Institute Physician. I'm also the Worthington and Margaret Collette Professor of Medicine in hematologic oncology at Harvard Medical School.
I had the pleasure of presenting the progression-free survival results from the ALPINE trial. Now, the ALPINE trial is comparing two Bruton tyrosine kinase inhibitors. And you'll remember that Bruton tyrosine kinase inhibitors, or BTK inhibitors, have transformed the therapy of CLL in the last decade. And there's the first-in-class drug, ibrutinib (Imbruvica), which is very effective but has significant side effects. And zanubrutinib (Brukinsa) was developed with the intention of both being potentially more effective, by hitting BTK harder than ibrutinib, and also safer, having fewer off-target effects and fewer side effects.
So this study, we compared them head-to-head in patients with relapsed CLL. Most of them had one prior chemotherapy regimen, and now they were on their second-line therapy. And we found that the response rate with zanubrutinib was better than ibrutinib, and zanubrutinib kept the disease away longer, compared to ibrutinib. This was a particularly dramatic effect in the highest-risk group of patients, those with 17p, but there was actually a 22% improvement in keeping the disease away at two years by zanubrutinib, compared to ibrutinib. And in the overall group, it was important, too, at 12%.
We also found that zanubrutinib was safer. There were fewer patients who had to stop the drug due to adverse events or hold the drug due to adverse events. And the cardiac profile, in particular, we worry a lot about, because we know there are significant cardiac effects with ibrutinib. But the rates of atrial fibrillation were much lower with zanubrutinib, 5%, versus 13% with ibrutinib, and there were fewer cardiac serious adverse events. Only one drug discontinuation with zanubrutinib for a cardiac event, and no deaths due to a cardiac event. Whereas, on ibrutinib, there were actually six deaths due to a cardiac event.
So this is really very exciting news. Zanubrutinib is both more effective and safer than ibrutinib and will be our new standard-of-care BTK inhibitor.
