Zanubrutinib Monotherapy in Patients With Del(17p) and Treatment-Naive CLL/SLL (SEQUOIA Arm C)

The discussion centers on the importance of biomarker testing in the treatment of CLL, particularly for patients with high-risk genetic features such as TP53 mutations or deletion 17p. Biomarker testing is emphasized as a critical step before initiating treatment, providing necessary chromosomal and molecular data through tools such as fluorescence in situ hybridization, karyotyping, and mutation panels. Testing for immunoglobulin heavy chain variable region status is also considered essential. These diagnostics help stratify patients and inform treatment choices, especially since some abnormalities, such as TP53 mutations, are associated with poor responses to traditional chemoimmunotherapy.

The conversation shifts to a detailed overview of the SEQUOIA trial, which investigated a targeted monotherapy in patients with CLL. Importantly, the study design included a specific cohort (Arm C) for patients with deletion 17p, known to be a high-risk group. These patients received a targeted agent rather than chemoimmunotherapy, aligning with evolving clinical understanding. The cohort included 111 patients—making it the largest dedicated 17p deletion group in the frontline setting. Results from this arm showed promising efficacy, with patients receiving 160 mg of the agent until progression, unacceptable toxicity, or death. This 5-year update presented at the American Society of Clinical Oncology showed significant progress in addressing high-risk CLL.

The outcomes from the SEQUOIA trial were notably positive. Five-year progression-free survival (PFS) for patients with TP53 abnormalities was reported at 72.2%, which compares favorably with patients with wild-type disease, who showed around 75% PFS. Overall survival had not been reached at the time of reporting, indicating continued positive responses. High overall response rates were seen, consistent with expectations for the targeted therapy used. The data suggest that even in high-risk groups, long-term disease control is achievable with monotherapy, supporting its use as a frontline treatment for patients with TP53 mutations or deletion 17p.