Deletions of the short arm of chromosome 17 (del(17p)) are found in 5% to 8% of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) at the time of diagnosis. This includes the loss of the tumor suppressor gene TP53 that resides on the short arm (p) of the 17th chromosome. This used to be a dreaded diagnosis for patients with CLL / SLL since it is associated with resistance to chemoimmunotherapies and worse outcomes. However, targeted therapies provide new options for patients with del(17p). One new targeted therapy is zanubrutinib, a next-generation BTK inhibitor currently being tested in clinical trials for CLL / SLL. It is much more specific for BTK than ibrutinib, so researchers hope it will have fewer side effects.
At the American Society of Hematology (ASH) 2021, Dr. Alan Skarbnick, Director of the CLL program at Novant Health Cancer Institute in Charlotte, NC, interviewed Dr. Constantine Tam, a hematologist at the Peter McCallum Cancer Center in Melbourne, Australia. They discussed the SEQUOIA trial, a phase 3 trial testing the efficacy of zanubrutinib as a first-line treatment in patients with CLL / SLL.
Takeaways:
- The SEQUOIA trial is a global phase 3, open-label, randomized study of zanubrutinib as a first-line treatment in patients with previously untreated CLL / SLL. The comparator group received the chemoimmunotherapy bendamustine plus rituximab.
- Thus far, in patients without del(17p), zanubrutinib significantly improves progression-free survival compared with bendamustine plus rituximab. You can learn more about these results here.
- Patients with del(17p) do not respond well to chemoimmunotherapy. Thus, it would be unethical to randomize them to bendamustine plus rituximab.
- Initially, the SEQUOIA trial assigned patients with del(17p) to Arm C, where they received open-label zanubrutinib, and they did quite well on it.
- When Arm C was full, the researchers opened Arm D, which offers zanubrutinib plus venetoclax to patients with del(17p).
- It is still very early on in the trial. Still, thus far, it appears to be feasible to give patients zanubrutinib plus venetoclax with no unexpected toxicities, and it has been well-tolerated.
- Because it is so early on in the trial, researchers do not have minimal residual disease results yet, but those should be forthcoming as the trial progresses.
Conclusions:
These early results are encouraging, especially for a hard-to-treat patient population. We are happy to see patients with del(17p) getting a chance to be included in new clinical trials with novel agents. We look forward to learning more about the efficacy of zanubrutinib plus venetoclax as this trial progresses.
Please enjoy this interview with Dr. Tam from the ASH meeting held in December 2021 in Atlanta, GA.
You can read the actual abstract here: Zanubrutinib in Combination with Venetoclax for Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with del(17p): Early Results from Arm D of the SEQUOIA (BGB-3111-304) Trial
Take care of yourself first.
Ann Liu, PhD
