Hypofractionated Radiotherapy plus GM-CSF, Pomalidomide and Glofitamab for Newly Diagnosed PCNS-DLBCL

Inclusion Criteria:

1. Written informed consent must be obtained before any study-related procedures.
2. Age ≥18 years, regardless of sex, with an expected survival time \>3 months.
3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL).
4. Newly diagnosed patients with primary central nervous system diffuse large B-cell lymphoma (PCNSL).
5. No previous treatment with bispecific antibodies.
6. B-cell non-Hodgkin lymphoma with at least one measurable lesion according to RECIST 1.1 criteria, or detectable abnormal monoclonal B cells by cerebrospinal fluid (CSF) flow cytometry.
7. Adequate organ function meeting the following laboratory criteria:

   * Total bilirubin ≤1.5 × upper limit of normal (ULN);
   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN;
   * Serum creatinine ≤1.5 × ULN and creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula);
   * Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN.
8. Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first dose of study treatment (Cycle 1 Day 1). If urine pregnancy testing cannot confirm a negative result, a serum pregnancy test is required. Women of non-childbearing potential are defined as those who are postmenopausal for ≥1 year or have undergone surgical sterilization or hysterectomy.
9. All participants with reproductive potential (male or female) must use highly effective contraception with a failure rate \<1% per year during treatment and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).

Exclusion Criteria:

1. Loss of CD20 expression in B-cell non-Hodgkin lymphoma.
2. Active acute or chronic hepatitis B or hepatitis C infection, including:

   * HBV DNA \>2,000 IU/mL or \>10⁴ copies/mL without willingness to receive regular antiviral therapy;
   * HCV RNA \>10³ copies/mL;
   * Concurrent positivity for HBsAg and anti-HCV antibody.
3. Receipt of anti-hematologic malignancy therapy within 2 weeks or within 5 pharmacokinetic half-lives before treatment initiation, whichever is longer.
4. Inadequate bone marrow reserve, defined as platelet count \<30 ×10⁹/L or absolute neutrophil count \<1.0 ×10⁹/L.
5. Clinically significant pulmonary diseases, including:

   * Chronic obstructive pulmonary disease (COPD) with FEV1 \<50% of predicted value;
   * Moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any severity.
6. Uncontrolled hypertension despite optimal medical management (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg), history of hypertensive crisis, or hypertensive encephalopathy.
7. Symptomatic congestive heart failure (NYHA class II-IV), symptomatic or poorly controlled arrhythmias, congenital long QT syndrome, or corrected QT interval (QTc) \>500 ms (Fridericia correction).
8. Receipt of hypofractionated radiotherapy within 4 weeks before the first treatment. Patients receiving radiotherapy \>4 weeks before enrollment must have no ongoing radiation-related toxicities, no requirement for corticosteroids, and no evidence of radiation pneumonitis, hepatitis, enteritis, or other radiation-related complications.
9. Difficulty swallowing oral medications.
10. History or presence of pulmonary fibrosis, interstitial lung disease, pneumoconiosis, drug-induced pneumonitis, or severe pulmonary dysfunction.
11. HIV infection (positive HIV-1/2 antibody) or known syphilis infection.
12. Presence of unhealed wounds, fractures, gastric or duodenal ulcers, persistent positive fecal occult blood test, ulcerative colitis, or other conditions associated with risk of gastrointestinal bleeding or perforation as determined by the investigator.
13. Active or uncontrolled severe infection, including severe infection requiring hospitalization due to infection, bacteremia, or severe pneumonia within 4 weeks before the first dose.
14. Major surgery or significant traumatic injury within 4 weeks before the first dose.
15. Use of traditional Chinese medicine with antitumor indications within 2 weeks before the first dose.
16. Known hypersensitivity to any component of bispecific antibodies or GM-CSF preparations.
17. Receipt of treatment in another clinical trial within 4 weeks before the first dose.
18. Pregnant or breastfeeding women.
19. Active autoimmune disease or history of autoimmune disease, including but not limited to autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, and nephritis. Patients requiring medical intervention with bronchodilators for asthma are excluded. The following conditions are permitted: vitiligo, psoriasis, alopecia, or controlled type I diabetes not requiring systemic treatment, and hypothyroidism controlled with hormone replacement therapy.
20. Any other acute or chronic disease, psychiatric condition, or abnormal laboratory finding that may:

    * Increase the risk associated with study participation or administration of study treatment;
    * Interfere with interpretation of study results;
    * Render the patient unsuitable for participation according to the investigator's judgment.