Pirtobrutinib Plus Methotrexate-Based Chemoimmunotherapy for Systemic DLBCL With CNS Involvement

Prior treatment

• Contraindication to any drug in the treatment regimen.
• Documented prior history of neurological or psychiatric disorders; or history of psychotropic substance abuse or illicit drug use.

Other illness

• History of active liver disease, including viral or other hepatitis, or liver cirrhosis. (Active hepatitis B is defined as HBV-DNA above the upper limit of normal; active hepatitis C is defined as positive HCV antibody. Subjects with positive HCV antibody but negative HCV-RNA are eligible for enrollment.)
• Human immunodeficiency virus (HIV) infection.
• Congestive heart failure (New York Heart Association \[NYHA\] functional class \> 2); medical history of acute myocardial infarction, unstable angina pectoris, stroke, or transient ischemic attack within the preceding six months.

Lab values

• Congenital long-QT syndrome, or QTc \> 480 ms. (Note: QTc interval shall be calculated by the Fridericia's formula: QTcF = QT/(RR)\^0.33.)

Other

• Patients meeting any one of the following criteria will be excluded from this study:
• Pregnant or breastfeeding women, or subjects planning to become pregnant during the study period.

• Patients must satisfy all of the following conditions to be enrolled in this study:
• 1.Fully understand the study and voluntarily provide written informed consent. 2.Age: 14-80 years old. 3.Estimated survival of more than 3 months as judged by the investigator. 4.Histologically or cytologically / flow-cytometry confirmed B-cell-derived diffuse large B-cell lymphoma (DLBCL).
• 5.Central nervous system (CNS) involvement: diagnosis is established if any one of the following is present: symptoms related to CNS involvement, abnormal imaging findings, or pathological evidence (positive cerebrospinal fluid (CSF) cytology, positive biopsy of brain parenchymal lesions, or positive CSF-ctDNA).
• 6.Non-hematologic toxicities related to prior therapy shall have recovered to Grade 1 or baseline (per NCI-CTCAE Version 5.0), alopecia excluded.
• 7.Bone marrow and organ function meet the following criteria (no blood transfusion, G-CSF administration, or pharmacologic correction within 14 days prior to screening):
• Bone marrow function: absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; platelet count ≥ 50 × 10⁹/L; hemoglobin ≥ 60 g/L.
• Liver function: serum total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN in the presence of liver involvement); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5.0 × ULN in the presence of liver involvement).
• Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• Renal function: serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 30 mL/min.
• Calculationformula(Cockcroft-Gault):Male:Cr(mL/min) = (140 - age) × bodyweight (kg) / (72 × serum creatinine(mg/dL))Female:Cr(mL/min) = (140 - age) × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)) 8.Women of child-bearing potential and men with reproductive potential have no plan for conception with their partners during the study and for 3 months after treatment discontinuation. They must adopt one of the following effective contraceptive measures throughout the study period and for 3 months after treatment discontinuation: abstinence, physical contraception (e.g., sterilization, condoms), or hormonal contraceptives initiated at least 3 months prior to the first study drug administration. Male subjects shall refrain from sperm donation from treatment initiation through 3 months after treatment discontinuation. The patient or legal guardian voluntarily signs the informed consent form.
  • 9.Good compliance and willingness to adhere to visit schedules, drug administration plans, laboratory tests, and other study procedures.