a multi-center clinical study of zanubrutinib in combination with first-line chemoimmunotherapy in patients with grade 3a high-risk follicular lymphoma

Conditions: Follicular Lymphoma

Summary: background： at present, there is controversy about whether fl3a is treated as fl or dlbcl. relevant studies have shown that compared with patients with fl3a grade 1\~2, they have unique immunohistochemical characteristics, and there are some differences in clinical features and outcomes. in patients with fl3a, the ki-67 index is higher, the recurrence rate is higher, there is more histologic transformation, the prognosis is worse, and the likelihood of lymphoma-related death is higher. bruton's tyrosine kinase (btk) is a key kinase in the b-cell signaling pathway, and studies have shown that btk inhibitors including zanubrutinib combined with traditional immunochemotherapy regimens may have a synergistic effect in the treatment of b-cell malignancies, and the combination has become one of the current clinical research directions. aim: to assess the efficacy and safety of zanubrutinib in combination with first-line immunochemotherapy in high-risk patients with fl3a.

bruton's tyrosine kinase (btk) is a key kinase in the b-cell signaling pathway, and its abnormal activation leads to abnormal activation of the b-cell receptor signaling pathway, b-cell malignant proliferation, and lymphoma. there is controversy about whether fl3a is treated as fl or dlbcl. relevant studies have shown that compared with patients with fl3a grade 1\~2, they have unique immunohistochemical characteristics, and there are some differences in clinical features and outcomes. in patients with fl3a, the ki-67 index is higher, the recurrence rate is higher, there is more histologic transformation, the prognosis is worse, and the likelihood of lymphoma-related death is higher. bruton's tyrosine kinase (btk) is a key kinase in the b-cell signaling pathway, and studies have shown that btk inhibitors including zanubrutinib combined with traditional immunochemotherapy regimens may have a synergistic effect in the treatment of b-cell malignancies, and the combination has become one of the current clinical research directions. the recent study is to assess the efficacy and safety of zanubrutinib in combination with first-line immunochemotherapy in high-risk patients with fl3a.

Eligibility criteria:
inclusion criteria: * 1. age 18-70 years old (including 18 years old and 70 years old), ecog score 0-2 points; 2. confirmed diagnosis of follicular lymphoma with pathological grade of 3a (pathological report of three months before enrollment is acceptable) (note: if there is any doubt about the pathological diagnosis, a domestic third-party consultation can be organized); 3. treatment-naïve patients with indications for treatment; 4. meet at least one of the criteria for high tumor burden in gelf; 5. have not received other tumor-related treatments in the past; 6. acceptable hematological indexes, no contraindications to chemotherapy; 7. liver function: tbil≤1.5×uln; alt or ast ≤2.5×uln; alkaline phosphatase ≤3×uln in patients with non-bone invasion; 8. renal function: serum creatinine ≤1.5×uln; 9. female and male patients of childbearing potential and their spouses are willing to use adequate contraception throughout the study period, and female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose; 10. subjects voluntarily participated in the clinical trial, signed the informed consent form, and cooperated with the follow-up. exclusion criteria: * 1. refusal to collect blood specimens; 2. previous allergy to any of the medications in the regimen; 3. pregnant and lactating women; 4. significant illness that, in the opinion of the investigator, can cause trial interference; 5. combined with other tumors; 6. presence of contraindications related to the treatment of the drug in the protocol; 7. those with severe mental illness; 8. participating in other clinical trials; 9. prior treatment with anti-tumor therapy (such as radiotherapy, chemotherapy, hormonal therapy, biological therapy, immunotherapy); 10. other serious diseases that may limit the subject's participation in this trial, such as: uncontrolled diabetes mellitus; severe cardiac insufficiency (nyha classification ii or above); acute coronary syndrome within the past 6 months; coronary revascularization such as stenting, coronary artery bypass surgery, and other heart and large vessel related surgeries in the past 6 months; severe arrhythmias include frequent premature ventricular episodes, ventricular tachycardia, rapid atrial fibrillation/atrial flutter, and severe bradycardia. uncontrolled hypertension: systolic blood pressure \> 150 mmhg, diastolic blood pressure \> 100 mmhg. gastric ulcer (gastric ulcer judged by the investigator to be at risk of perforation); active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, sjögren's syndrome, autoimmune thrombocytopenia, etc.); severe respiratory diseases (such as obstructive pulmonary disease and history of bronchospasm), etc.; 11. in the opinion of the investigators, it is not suitable for enrollment; 12. hepatitis b core antibody (hbcab) positive and peripheral blood hepatitis b virus (hbv) dna titer test is not within the normal reference value; those who are positive for hepatitis c virus (hcv) antibody and positive for hepatitis c virus (hcv) rna in peripheral blood; those who are positive for human immunodeficiency virus (hiv) antibodies; those who test positive for syphilis.