SEQUOIA Study Focuses on High-Risk Deletion 17p Population in CLL

Jennifer R. Brown, MD, PhD, director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, discusses the patient population of the SEQUOIA trial (NCT03336333) of zanubrutinib (Brukinsa) and venetoclax (Venclexta) for patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Patients with the deletion of chromosome 17p13.1 (del[17p]) are the highest-risk subgroup in CLL, according to Brown. In other CLL study populations not selected for prognostic factors, only about 10% of patients have del(17p) mutations, which is not enough to reliable assess their response to therapies, Brown says.

The phase 3 SEQUOIA trial’s Arm D only enrolled patients with del(17p) based on central verification with fluorescence in situ hybridization (FISH). The median frequency of the 17p mutation was 81.5%, and 85.3% did not have an IGVH mutation.

This arm is planned to enroll 80 patients, and 35 have been enrolled as of June 1, 2021. They are to receive zanubrutinib and venetoclax until they reach disease progression, undetectable minimal residual disease, or unacceptable toxicity. Interim results presented at the American Society of Hematology (ASH) 2021 Annual Meeting & Exposition reported an 96.8% overall response rate in this arm.

TRANSCRIPTION:

0:08 | The patient population is restricted to patients with del(17p), which are our highest-risk subgroup in CLL, and I think it's a particularly important feature of this study because most of the studies that have been done and are being reported at ASH this year enrolled [patients with] CLL regardless of prognostic factors. And as a result, there are only often about 10% of patients with del(17p) enrolled in those studies frontline, which leaves us with maybe 5, 10, or 20 patients to evaluate. So it's really hard to figure out what the best regimen is for these patients who have the greatest remaining unmet medical need in CLL.

So, that's a very important feature of this study, and I think the patient population is pretty representative. They have a high percentage 17p by FISH. They're almost all unmutated for IGVH, and they also mostly have a very complex karyotype, which is something else that goes with del(17p). So the patient population looks like fairly typical del(17p) patients, namely high-risk, and I think that's very good. At this point, the study follow-up is still relatively short, but over time, that will be very important to assess.