Constantine Si Lun Tam, MD, FRACP, FRCPA, MBBS, on CLL/SLL: First-Line Zanubrutinib Monotherapy in Patients With del(17p)

We've decided to present the long-term data of zanubrutinib monotherapy in patients with 17p deletion CLL. Historically, 17p deletion CLL is a horrible disease to treat. The average survival is less than three years. But the BTK inhibitors have really made a big difference in this disease. Now, after BTK inhibitors, zanubrutinib is a next-generation drug. It's got better penetration, better drug coverage, and in head-to-head comparison with ibrutinib in a study called ALPINE, zanubrutinib has been proven to be more effective and has fewer side effects. In this particular study, we decided to look at zanubrutinib in the frontline, and the actual study is a randomized study between bendamustine and zanubrutinib. Those results have been previously reported. Zanubrutinib is better, but for patients in that study who were screened and found to have 17p deletion at baseline, it's unethical to randomize those patients to bendamustine-rituximab, so they entered what we call arm C, which is the non-randomized arm where all patients received zanubrutinib monotherapy because they carried 17p deletion. This turned out to be the largest prospective cohort of patients ever treated for 17p deletion CLL with anything, and the experience here with 110 patients vastly outnumbers the experience with ibrutinib and acalabrutinib combined. So we're excited to share the mature data in this large cohort of patients. Essentially, the headline results are that the response rate is very high—97%—but the most important thing is that at five-year follow-up, 72.2% of patients remain in remission on progression-free survival. And if you compare with the same study with a different arm in the SEQUOIA study where patients without 17p were given zanubrutinib, their PFS was 75%, so 75% without 17p, 72% with 17p, suggesting that zanubrutinib is actually very successful in neutralizing the previously very adverse risk of this population. The overall survival at five years is actually 85%, which, as I mentioned before, before we had BTK inhibitors, the overall survival for these patients was less than three years. So really, I think that underscores and celebrates how far the field has come in treating 17p deletion CLL. I think the important thing about this data set is that this is the biggest data set with mature follow-up in 17p CLL. It shows us that zanubrutinib works irrespective of your 17p status and that the outcomes are excellent and really set a new benchmark for the treatment of 17p deletion CLL in the frontline.