QLS4131 Plus Isa-V-CHOP in Newly Diagnosed, HIV-Negative PBL: A Single-Center, Single-Arm, Phase II Study (PBL-001)

Inclusion Criteria:

1. Understands and voluntarily signs the informed consent form (ICF);
2. Age ≥18 years;
3. Histopathologically confirmed plasmablastic lymphoma (PBL);
4. Positive BCMA or GPRC5D expression: BCMA or GPRC5D expression on tumor cells confirmed by immunohistochemistry (IHC) or flow cytometry;
5. Treatment-naive or having received no more than 1 cycle of prior systemic therapy (e.g., CHOP, EPOCH);
6. Measurable disease (unless only bone marrow lesions are present), defined as at least one lesion with a longest diameter ≥1.5 cm as measured by CT or PET-CT;
7. ECOG performance status 0-2 (may be relaxed to 3 for elderly/frail patients if organ function permits);
8. Liver function tests meeting the following criteria: total bilirubin ≤1.5× upper limit of normal (ULN), unless due to Gilbert's syndrome or of non-hepatic origin; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (except for liver function impairment caused by tumor invasion);
9. Renal function tests meeting the following criterion: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula);
10. Blood routine tests within 14 days before the start of screening meeting the following criteria (except in patients with bone marrow involvement): absolute neutrophil count ≥1.0×10⁹/L and platelet count ≥75×10⁹/L; Expected life expectancy ≥2 months as judged by the investigator.

Exclusion Criteria:

1. Diagnosis or treatment of a malignancy other than PBL within 1 year before enrollment (except for cases treated with surgery alone and considered cured);
2. Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) or CAR-T therapy;
3. History of epilepsy or other central nervous system disorders;
4. Other severe medical conditions that could affect the study (e.g., myocardial infarction within 6 months, uncontrolled diabetes, other severe cardiopulmonary diseases, etc.); the determination is at the investigator's discretion;
5. Human immunodeficiency virus (HIV) infection;
6. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as HBV-DNA or HCV-RNA above the upper limit of detection, with or without abnormal liver function. If a patient had active HBV infection at initial diagnosis and converted to inactive HBV infection after anti-HBV treatment, the patient may be enrolled in this study provided adequate anti-HBV therapy;
7. Pregnant or lactating women, or women of childbearing potential not using contraceptive measures;
8. Major surgery (e.g., requiring general anesthesia) within 2 weeks before enrollment, or not expected to fully recover from surgery, or surgery planned during the planned study participation period. Note: subjects with planned surgical procedures under local anesthesia may participate in the study;
9. Hypersensitivity to the drugs used;
10. Any active severe psychiatric illness, medical illness, or other symptoms/conditions that, as judged by the investigator, may affect treatment, compliance, or the ability to provide informed consent.