Zanubrutinib monotherapy or zanubrutinib plus obinutuzumab (ZO) followed by zanubrutinib monotherapy led to high rates of overall and complete response in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL). Researchers presented the findings at the ASH Annual Meeting.
The researchers presented findings from two studies: a phase 1/2 AU-003 study, which evaluated zanubrutinib monotherapy in patients with various B-cell malignancies, including CLL/SLL, and a phase 1b GA-101 study, which evaluated six cycles of the ZO combination, followed by continuous zanubrutinib monotherapy in patients with CLL/SLL and follicular lymphoma. Upon study completion, eligible patients could enroll in a long-term extension for continued zanubrutinib treatment.
At study enrollment, the population of 170 patients had a median age of 68 years (range, 24–87), and 75.3% had relapsed/refractory (R/R) CLL/SLL. In addition, 17.1% had Del(17p), and 18.2% had TP53 mutation. As of April 15, 2024, the median follow-up was 78.1 months (range, 5.3–106.9), and the median treatment duration was 67.9 months (range, 0.8–106.9).
In AU-003, which studied zanubrutinib monotherapy, overall response rates were 100% in treatment-naïve patients and 94.2% in patients with R/R CLL/SLL. Rates of complete response (CR)/CR with incomplete bone marrow recovery (CRi) were 36.4% and 25.2%, respectively. In GA-101, which studied ZO, overall response rates were 100% among treatment-naive patients and 92% among patients with R/R CLL/SLL. CR/CRi rates were 60% and 36.0%, respectively.
Regarding safety, grade 3 or higher and serious treatment-related adverse events occurred in 84.1% of patients in the parent studies and 69.4% in the extension. This led to treatment discontinuation in 13.5%, dose reductions in 12.9%, and death in 7.1%. Adverse events of note were atrial fibrillation/flutter and hypertension.
“With a median follow-up of 6.5 years, the durability of these responses was demonstrated. The tolerability/safety profile of zanubrutinib, alone and in combination with obinutuzumab, remained favorable,” concluded the authors, led by Constantine S. Tam, MD, MBBS, of Alfred Hospital and Monash University, in Melbourne, Australia.
https://ash.confex.com/ash/2024/webprogram/Paper200363.html
Reference
Tam CS, Opat SS, Merriman EG, et al. Deep and sustained responses in patients with CLL treated with zanubrutinib or zanubrutinib + obinutuzumab in phase 1/2 AU-003 and phase 1b GA-101 studies: a report from the Zanubrutinib Extension Study. Abstract #3255. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7–10, 2024; San Diego, California.
