To explore the application of HiR (Zebtorizumab, Lenalidomide) + X (targeted drug) guided by NGS molecular typing, the aim is to assess the therapeutic efficacy and safety in newly diagnosed unfit or frail elderly patients with DLBCL aged ≥70 years, and to investigate the genetic subtypes that may benefit from HiR-X.

Inclusion Criteria:

1. Age ≥ 70 years;
2. ECOG score 0-3;
3. Rated as "unfit" or "frail" on the simplified geriatric assessment (sGA);
4. Histologically confirmed CD20-positive diffuse large B-cell lymphoma [diagnostic criteria according to WHO 2016], excluding transformed type 2 DLBCL;
5. Previously untreated, newly diagnosed patients;
6. Cardiac, hepatic, and renal function: creatinine < 2 times the upper limit of normal (ULN); ALT (alanine aminotransferase) / AST (aspartate aminotransferase) < 2.5 x ULN; total bilirubin < 2 x ULN;
7. At least one measurable lesion;
8. Intolerance to standard CHOP chemotherapy regimen or unwillingness to receive chemotherapy;
9. Sufficient understanding and voluntary signing of the informed consent form.

Exclusion Criteria:

1. Patients with central nervous system involvement at the onset of the disease;
2. Known human immunodeficiency virus (HIV) infection;
3. Pregnant or lactating women;
4. Other tumors requiring treatment;
5. Uncontrolled active infection;
6. Active hepatitis with HBV-DNA copy number unable to be controlled within 2000/mL despite antiviral treatment;
7. Individuals who cannot understand, comply with the study protocol, or sign the informed consent form.