Follicular lymphoma (FL) remains an incurable indolent B-cell lymphoma for many patients, and although rituximab-based chemoimmunotherapy can achieve high initial response rates, a substantial proportion of patients experience early progression, including POD24, which is associated with poor long-term outcomes. This underscores the need for more effective and better-tolerated frontline treatment strategies, particularly chemotherapy-free approaches. The present study is based on a strong biologic rationale that simultaneously targets two key pathogenic mechanisms in FL: aberrant B-cell receptor signaling and impaired apoptosis driven by BCL2 overexpression. Zanubrutinib, a next-generation BTK inhibitor, has shown clinical activity with a favorable safety profile in FL, while sonrotoclax, a potent and highly selective next-generation BCL2 inhibitor, has demonstrated promising preclinical and early clinical activity. In combination with rituximab, this chemotherapy-free triplet regimen may produce deeper and more durable remissions while maintaining manageable toxicity, and therefore has the potential to expand frontline treatment options and improve outcomes for patients with previously untreated FL.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Zanubrutinib oral administration, Sotoclax oral administration, Rituximab intravenous injection.
Sun Yat-sen Universitiy Cancer Center
Guangzhou, Guangdong, China
CR rate
Complete response rate
Time frame: Up to 6 months
ORR
Overall response rate
Time frame: Up to 6 months
DoR
Duration of response
Time frame: Up to 3 years
PFS
Progression free survival
Time frame: Up to 3 years
OS
Overall survival
Time frame: Up to 3 years
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