Relmacabtagene Autoleucel Combined With Autologous Hematopoietic Stem Cell Transplantation, Orelabrutinib, and Sintilimab for Primary Central Nervous System Lymphoma

Inclusion criteria

1.18-60 years 2.ECOG performance status 0-2 3.No prior treatment with CAR-T cell therapy or autologous stem cell transplantation (ASCT) 4.Expected survival ≥ 3 months 5.No history of malignancy (except for in situ carcinoma or other indolent malignancies), or inactive malignancy with treatment completed >1 year ago 6.Histopathologically confirmed PCNSL (lymphoma confined to the brain without systemic involvement, with histopathological type being diffuse large B-cell lymphoma, or systemic lymphoma with central nervous system involvement and histopathological type being diffuse large B-cell lymphoma) 7.Refractory disease is defined as failure to achieve complete remission after first-line therapy (excluding intolerance to first-line therapy), including: Progressive disease (PD) as best response to first-line therapy, or Stable disease (SD) as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP), or Residual disease after at least 6 cycles of first-line therapy, or relapse within 12 months after completing first-line therapy 8.Relapsed disease is defined as recurrence after achieving complete remission following first-line therapy, occurring within 12 months after treatment completion 9.Positive CD19 expression by immunohistochemistry 10.No contraindications for CAR-T cell therapy or ASCT 11.No concurrent use of other anti-tumor therapies during this treatment; bisphosphonates for bone metastases and symptomatic supportive treatments are allowed 12.Able to understand the study and provide signed Informed Consent Form

Exclusion criteria

• Pregnant or lactating women
• Any uncontrolled medical condition (including active infection, uncontrolled diabetes, severe cardiac, hepatic or renal insufficiency, interstitial pneumonia, etc.)
• Use of systemic corticosteroids within 7 days before CD19 CAR-T cell infusion (except ≤ 5 mg/day dexamethasone or equivalent doses of other corticosteroids)
• Prior exposure to ≥ 2 of the following agents with documented resistance: orelabrutinib, fotemustine, carmustine, thiotepa, or PD-1/PD-L1 inhibitors
• History of autoimmune disease
• Presence of cachexia or any other contraindication to chemotherapy
• Active, uncontrolled infection
• History of poorly controlled psychiatric disorder
• Any condition that, in the opinion of the investigator, would preclude safe participation in this trial