Efficacy and Safety of Zanubrutinib Monotherapy in Real-World Chinese CLL/SLL Patients

Background: BTK inhibitors (BTKis) have become the standard-of-care therapies for both frontline and relapsed/refractory Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL). As a second-generation BTKi, zanubrutinib has demonstrated superior efficacy and a favorable safety profile in head-to-head clinical trials compared to the first-generation BTKi, ibrutinib. The objective of this study was to assess the real-world efficacy of single-agent zanubrutinib in patients with CLL/SLL. This study presents the largest multicenter, real-world data on zanubrutinib monotherapy in Chinese CLL/SLL patients (NCT06489184).

Methods: This was a retrospective observational study of adult patients with CLL/SLL who initiated single-agent zanubrutinib treatment between June 2014 and March 2024 at fourteen sites across China, followed up through April 1, 2024. All patients had at least one month of follow-up. Duration of treatment (DOT), reasons for discontinuation, real-world progression-free survival (rwPFS), overall survival (OS), and dose reduction were reported.

Results: A total of 322 patients received zanubrutinib monotherapy in the first line (1L, n = 180), second line (2L, n = 105), and third line or greater (≥3L, n = 36), and included one patient for whom the treatment line was unknown. The median (range) age of patients was 64.7 (34-92) years, and most patients were male (63%). Moreover, del(17p) or TP53 mutation was found in 62/266 (23.3%) tested patients. Unmutated IGHV was reported in 116/222 (52%).

After a median (range) follow-up of 25.0 (1.0-119.3) months, 20.3% of patients discontinued zanubrutinib, mostly due to progressive disease (31 patients, 9.6%). Seventeen patients (5.3%) discontinued treatment due to patient preference, and 14 patients (4.3%) discontinued treatment due to adverse events (AEs). The most common AEs leading to discontinuation were infections (including COVID-19) (1.6%) and bleeding (1.3%). No cardiac AEs led to discontinuation; only one patient discontinued treatment due to blood pressure elevated. A total of 255 patients were still on zanubrutinib treatment.

The 24-month duration of treatment rate was 84.4% in all patients (1L: 88.4%, 2L: 87.4%, ≥3L: 64.3%). The 24-month rwPFS rates were 95.9% for 1L, 90.8% for 2L, and 78.9% for ≥3L, while the OS rates were 97.4%, 96.3%, and 89.1%, respectively.

Fifty-seven patients initiated zanubrutinib before June 2020 (when zanubrutinib was approved in China for CLL/SLL therapy on June 3, 2020), 12 patients in 1L, 30 patients in 2L, 15 patients in 3L, being patients from clinical trials. The median DOT of these patients was 71.6 months, and their median rwPFS were 109.6 months, 72-month rwPFS rate was 60.4%, the median OS has not been reached, and the 72-month OS rate were 86.3% .

Dose reduction due to AEs occurred in 12 patients; among them, 4 patients experienced platelet count decreased, 3 patients experienced bleeding, and 2 patients experienced cardiac AEs (one with palpitations and atrioventricular block first degree, and one with paroxysmal atrial tachycardia and atrial fibrillation).

Conclusion: The real-world efficacy of zanubrutinib monotherapy for CLL/SLL is consistent with clinical trials. These results strongly support zanubrutinib as a valuable treatment option for CLL/SLL patients, especially in those receiving first-line therapy, and discontinuation and dose reduction due to cardiac AEs are less common. Further investigation is warranted to fully elucidate the long-term benefits of zanubrutinib in the management of CLL/SLL.

No relevant conflicts of interest to declare.