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.
Willing to participate in the clinical study and signed informed consent.
Age ≥18 years, no gender restrictions.
Pathologically diagnosed with follicular lymphoma (Grade 1, 2, or 3a) and previously untreated.
Has at least one measurable or assessable lesion.
Known active central nervous system lymphoma or leptomeningeal disease.
Evidence of follicular lymphoma with transformation to diffuse large B-cell lymphoma.
Prior history of other malignancies other than follicular lymphoma (except for those with disease-free survival ≥5 years and assessed by the investigator as having low risk of recurrence).
History of allergy to the investigational drug, similar drugs, or excipients.