Sintilimab Plus Rituximab Followed by R-CHOP Regimen in Untreated PMBL

Participants will first receive sintilimab plus rituximab for 2 cycles, followed by interim PET-CT assessments. If patients achieve CR or CMR, they will continue to receive 2 courses of sintilimab plus rituximab, followed by 4 cycles of R-CHOP. Patients will receive 6 courses of R-CHOP if they do not achieve CR or CMR after 2 cycles of sintilimab plus rituximab. Patients will undergo PET-CT assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs. Total treatment cycles will not exceed 14 cycles

Inclusion criteria

• Voluntary participation in clinical study and fully understand, informed consent and sign informed consent form (ICF);
• Age ≥ 18 years and ≤ 75 years at the time of signing the ICF.
• treatment-naïve, no anti-lymphoma therapy.
• Primary mediastinal DLBCL was confirmed histopathologically at the study site.
• Lugano clinical stage I-IV.
• International Prognostic Score (IPI) 0-5.
• Available tumor tissue samples obtained by previous or fresh core needle aspiration or resection.
• ECOG score of 0-2.
• Expected survival greater than 12 months.
• Must have at least 1 evaluable or measurable lesion that meets the LYRIC 2016 response evaluation criteria for malignant lymphoma.
• Adequate organ and bone marrow function, no severe hematopoietic dysfunction and heart, lung, liver, kidney, thyroid dysfunction and immunodeficiency.
• Pulse oximetry values > 92% at rest.
• Women of childbearing potential (WOBCP) must have a negative serum pregnancy test within 7 days before the first dose; WOBCP or men and their WOBCP partners should agree to use effective contraception from signing the ICF until 6 months after the last dose of study drug.

Exclusion criteria

• Primary central nervous system lymphoma or secondary central nervous system involvement.
• previous treatment with immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4, etc.).

3 History of severe allergic or allergic reactions to humanized or murine monoclonal antibodies.

• Patients with active autoimmune diseases that require systemic treatment within the past two years; patients with autoimmune diseases that do not require systemic treatment within the past two years may be enrolled.

• Subjects requiring systemic glucocorticoid therapy or other immunosuppressive therapy for a condition within 14 days prior to starting study treatment [subjects are allowed to be treated with topical, ocular, intra-articular, intranasal, and inhaled glucocorticoids (with minimal systemic absorption); short-term (≤ 7 days) glucocorticoid prophylaxis (e.g., contrast agent allergy) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity due to contact allergens) is allowed]. Low dose steroid debulking therapy for large tumor burden may be excluded (prednisone 30 mg bid × 5 days or equivalent doses of other steroids are allowed).

• Other malignancies within the past 5 years, except for radically treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, breast carcinoma in situ, and cervical carcinoma in situ.

• Systemic anti-tumor therapy within 28 days before starting study treatment, including chemotherapy, immunotherapy, biological therapy (tumor vaccine, cytokines, or growth factors to control cancer), etc.

• Major surgery within 28 days or radiation therapy within 90 days prior to starting study treatment.

• Anti-cancer Chinese herbal medicine or Chinese patent medicine within 7 days prior to starting study treatment.

• Administration of live vaccines (except attenuated influenza vaccines) within 28 days prior to starting study treatment.

• Patients with known history of human immunodeficiency virus infection and/or acquired immunodeficiency syndrome.

• Patients with active chronic hepatitis B or active hepatitis C. Patients who are positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at screening must be further tested for hepatitis B virus (HBV) DNA titer (not more than 2500 copies/mL or 1000 IU/mL) and HCV RNA (not more than the lower limit of detection of the assay).

• Any active infection requiring systemic anti-infective therapy within 14 days prior to starting study treatment.

• Pregnant or lactating women. 15. Have uncontrolled concomitant disease. 19. Patients with a previous history of mental illness; those who are incapacitated or have limited behavioral ability.