Constantine Tam, MD, Alfred Hospital and Monash University, Melbourne, Australia, shares results from a 5-year follow-up of the SEQUOIA trial which evaluated the efficacy of zanubrutinib among patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), particularly among those with del(17p) CLL.

The results of this analysis demonstrated efficacy and safety for patients with chronic lymphocytic leukemia, regardless of del(17p) or other high-risk factors, and, Dr Tam stated, “With 5 years of mature follow-up, we have a progression-free survival, which is not different from patients without 17p deletion, and really highlights that zanubrutinib as a good treatment option in patients with CLL, irrespective of their prognostic factors, even if they have the poor prognostic factor of 17p deletion.”

Transcript:

Hi, I'm Constantine Tam. I'm from the Alfred Hospital and Monash University in Melbourne, Australia, and I'm here at ASCO 2025. I'm here to present the long-term data of zanubrutinib as a single agent therapy in patients with 17p deletion CLL.

By way of background, zanubrutinib is a next generation BTK inhibitor. It has been compared head-to-head against ibrutinib and been shown to be more effective and safer. The particular study that I'm presenting is a sub-study of the SEQUOIA registration study. Now SEQUOIA compared zanubrutinib against bendamustine rituximab and we have published in the past that zanubrutinib is superior to bendamustine rituximab. Patients who are enrolled at baseline and find to have a 17 P deletion are treated differently, and that's because it's not ethical to randomize these patients to bendamustine rituximab. Everyone who is found to have 17p deletion on the SEQUOIA study were enrolled into the so-called Arm C, which is a non-randomized arm, and all these patients receive standard zanubrutinib as a single agent.

As it turned out, Arm C was the largest cohort of patients with 17p deleted-CLL ever enrolled in the history of CLL, and we are reporting the long-term update from this cohort.

We have 110 patients, all of whom are older and FCR-unfit and all of them carry the 17p deletion. This is the worst of the worst. We now have a 5-year progression-free survival of 72% for these patients on zanubrutinib monotherapy.

How does this compare against historic results? Well for a start, we have Arm A of the same study, which gave zanubrutinib to patients without del(17p) CLL and their progression-free survival is 75%. So 75% without 17p deletion, 72% with 17p deletion, showing that zanubrutinib is actually neutralizing the adverse risk of 17p deletion. Even in this older unfit population, the overall survival is 85% at 5-years.

I was commenting that before I started using BTK inhibitors, the overall survival in this group of patients will be less than 3 years. We've gone from a median of less than 3 years to an overall survival of 85% at 5 years.

The adverse event in the older unfit subgroup is exactly as expected. For the younger subgroup, we have an atrial fibrillation rate of 8% and the hypertension rate of 20%.

In conclusion, what we have here is the most robust data set ever in 17p deletion CLL. The collective experience here is larger than that of ibrutinib and acalabrutinib together. With 5 years of mature follow-up, we have a progression-free survival, which is not different from patients without 17p deletion, and really highlights that zanubrutinib as a good treatment option in patients with CLL, irrespective of their prognostic factors, even if they have the poor prognostic factor of 17p deletion.

Source:

Tam C, Ghia P, Shadman M, et al. SEQUOIA 5-year follow-up in arm C: Frontline zanubrutinib monotherapy in patients with del(17p) and treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 7011.