CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Able to understand and voluntarily sign the informed consent form.
* Age 18 years or older, male or female.
* Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, or transformed follicular lymphoma (tFL).
* Eastern Cooperative Oncology Group performance status of 0 to 2.
* Has received commercial anti-CD19 CAR-T cell therapy, with informed consent obtained before Day 28 after CAR-T cell infusion.
* Prior anti-lymphoma therapy-related adverse events, especially CAR-T-related adverse events, have stabilized and recovered to Grade 1 or lower, except for clinically insignificant toxicities.

Exclusion Criteria:

* History of other malignancies, except non-melanoma skin cancer without recurrence for more than 3 years, carcinoma in situ, such as cervical, bladder, or breast carcinoma, or follicular lymphoma.
* Prior autologous or allogeneic hematopoietic stem cell transplantation.
* Active or suspected uncontrolled fungal, bacterial, viral, or other infection requiring intravenous treatment. Patients with uncomplicated urinary tract infection or uncomplicated bacterial pharyngitis may be enrolled if responding to active treatment.
* History of immunodeficiency, including human immunodeficiency virus infection; positive treponema pallidum antibody; active hepatitis B virus infection; or active hepatitis C virus infection.
* Current or prior history of benign central nervous system disease, such as seizure, cerebrovascular ischemia or hemorrhage, dementia, cerebellar disease, or any central nervous system-related autoimmune disease.
* Lymphoma involvement of the atrium or ventricle.
* Autoimmune disease requiring systemic immunosuppressive or immunomodulatory therapy within 2 years.
* History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment.
* Any comorbidity that may affect or interfere with safety or efficacy assessment.

主要终点：Complete response rate (CRR) · CRR is defined as the proportion of patients who achieve complete response according to the Lugano 2014 criteria at 6 months after initiation of pirtobrutinib maintenance therapy. · At 6 months after initiation of pirtobrutinib maintenance therapy
次要终点：Best complete response rate (bCRR)；Best objective response rate (bORR)；Objective response rate (ORR)；Duration of complete response (DoCR)；Duration of response (DOR)；Progression-free survival (PFS)；Overall survival (OS)；Incidence of adverse events (AEs) and serious adverse events (SAEs)

• Pirtobrutinib Maintenance After CAR-T Cell Therapy · EXPERIMENTAL · Patients will receive pirtobrutinib 200 mg orally once daily starting on Day 30 after commercial anti-CD19 CAR-T cell infusion. Pirtobrutinib maintenance therapy will be continued for 6 months unless disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria occur. Patients who do not achieve complete response after 6 months of maintenance therapy, or who achieve complete response with detectable ctDNA, may receive a second infusion of commercial CAR-T cells at the investigator's discretion.

This is a single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of pirtobrutinib as maintenance therapy in patients with relapsed or refractory B-cell lymphoma after commercial anti-CD19 CAR-T cell therapy.