Pola-R-CHP Plus Sonrotoclax in Untreated BCL2-High/Double-Hit LBCL

Inclusion Criteria:

* Patients with newly diagnosed large B-cell lymphoma confirmed by histopathology, CD20-positive, excluding central nervous system lymphoma;
* Patients aged 18 to 75 years;
* International Prognostic Index score of 2 to 5;
* Patients with high BCL-2 expression or double-hit lymphoma characteristics;
* No prior anti-tumor treatment of any type;
* Estimated survival time ≥ 6 months;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
* Measurable lesions confirmed by radiological examination, defined as: at least one lymph node lesion with the longest diameter \> 1.5 cm, or at least one extranodal lesion with the longest diameter \> 1.0 cm, and at least two accurately measurable perpendicular diameters;
* Patients or their legal representatives must provide written informed consent before conducting any study-specific examinations or procedures;
* No prior treatment for lymphoma (except glucocorticoids).

Exclusion Criteria:

* Prior solid organ transplantation or stem cell transplantation;
* Complicated with uncontrolled coagulation disorders, connective tissue diseases, severe infectious diseases, etc.;
* Suspected active or latent tuberculosis (confirmed by a positive interferon-gamma release assay);
* Any of the following abnormal laboratory test values (unless these abnormalities are all caused by the underlying lymphoma):
* Neutrophils \< 1.0×10⁹/L;
* Platelets \< 75×10⁹/L;
* Serum AST and ALT ≥ 2.5× upper limit of normal (ULN);
* Total bilirubin ≥ 1.5×ULN;
* Serum creatinine clearance \< 30 mL/min (calculated using the Cockcroft-Gault formula);
* Uncontrolled or significant cardiovascular diseases, including but not limited to:
* Left ventricular ejection fraction (LVEF) \< 50%;
* Primary cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, etc.;
* Clinically significant QTc prolongation, with QTc interval \> 470 ms (females) or 480 ms (males), second-degree type II atrioventricular block, or third-degree atrioventricular block;
* Current or past history of central nervous system (CNS) diseases, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative diseases. However, participants with a history of stroke who have not had a stroke or transient ischemic attack in the past 2 years and have no residual neurological deficits as judged by the investigator are allowed to participate in the study;
* Patients with mental illness or other patients known or suspected to be unable to fully comply with the study protocol;
* Patients infected with human immunodeficiency virus (HIV);
* History of other malignant tumors that may affect protocol compliance or interpretation of results:
* Participants with a history of cured basal or squamous cell carcinoma of the skin, melanoma, or carcinoma in situ of the cervix at any time before the study are eligible to participate;
* Participants with a history of untreated low-grade early-stage prostate cancer (Gleason score ≤ 6, Stage 1 or 2) at any time before the study are eligible to participate;
* Participants who received adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer for ≥ 2 years before enrollment are eligible to participate;
* Participants with any other malignant tumor cured by appropriate radical treatment and in remission without treatment for ≥ 2 years before enrollment are eligible to participate;
* History of immune-related adverse events following prior immunotherapy drug-related treatment, as follows: known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections (excluding onychomycosis) at study enrollment, or major infections within 4 weeks before the start of Cycle 1;
* Active hepatitis B virus (HBV) infection (positive result by PCR). For patients with positive HBsAg test results, HBV DNA test is required; if HBV DNA \< 10³ IU/ml, they can be enrolled. If HBsAg test result is negative but HBcAb test is positive (regardless of HBsAb status), HBV DNA test is also required; if HBV DNA \< 10³ IU/ml, they can be enrolled;
* Positive hepatitis C test result (serological test for hepatitis C virus \[HCV\] antibody):
* Eligibility to participate is only allowed if the PCR test result for HCV RNA is negative in patients with positive HCV antibody;
* Participants with a history of progressive multifocal leukoencephalopathy (PML);
* Currently pregnant or breastfeeding, or planning to become pregnant during the study or within 12 months after the last dose;
* Other concurrent and uncontrolled medical conditions that the investigator believes will affect the patient's participation in the study.