Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes
This is a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes. After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance. Efficacy and safety assessments will be performed per protocol. Tumor response will be assessed by site investigators according to the 2014 Lugano criteria, including determination of response status, date of response, and date of progression/relapse.
• Age ≥18 years at the time of signing informed consent. Histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) with MCD/BN2/N1 molecular subtypes defined by LymphGen classification.
⁃ Previously untreated (treatment-naïve). International Prognostic Index (IPI) score of 2-5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy ≥6 months. At least one measurable lesion in two dimensions, defined as a maximum diameter \>1.5 cm by CT or MRI.
⁃ Left Ventricular Ejection Fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO).
⁃ Adequate hematologic function (unless due to underlying disease, e.g., extensive bone marrow involvement, or splenomegaly secondary to splenic involvement deemed by the investigator to be caused by DLBCL; blood product transfusions are allowed), defined as follows:
⁃ Hemoglobin ≥9.0 g/dL within 7 days prior to first treatment, without packed RBC transfusion.
⁃ Absolute Neutrophil Count (ANC) ≥1.0 × 10⁹/L. Platelet count ≥75 × 10⁹/L. Female participants of childbearing potential: Must agree to abstain from heterosexual intercourse or use contraception, and agree not to donate ova.
⁃ Male participants: Must agree to abstain from heterosexual intercourse or use contraception, and agree not to donate sperm.