Efficacy and Safety of Sequential Autologous Hematopoietic Stem Cell Transplantation Combined With Tafasitamab, Lenalidomide, and Standard Immunochemotherapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma

Prior treatment

• Uncontrolled infectious disease within 4 weeks prior to enrollment;
• Participation in another clinical trial within 6 weeks prior to enrollment;
• Systemic use of corticosteroids within 4 weeks prior to enrollment (excluding patients using inhaled corticosteroids);

Other illness

• Active hepatitis B or C virus infection;
• Severe autoimmune disease or immunodeficiency disorder;
• History of allergy to macromolecular biologic drugs such as antibodies or cytokines;
• Psychiatric illness;
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for enrollment.

Lab values

• Pregnant (positive urine/serum pregnancy test) or lactating women;

Other

• Men or women with plans for conception within 1 year;
• Inability to guarantee effective contraceptive measures (e.g., condoms, contraceptives) within 1 year after enrollment;
• Substance abuse/dependence;

• Age ≥18 years;
• Pathologically confirmed diagnosis of relapsed or refractory DLBCL;
• Patients must meet the following criteria:
• Definition of relapsed or refractory: Refractory: Patients who did not achieve remission (≥PR) with the most recent systemic therapy; Relapsed/progressive: Patients who developed new lesions or experienced a ≥50% increase in existing lesions (based on the Lugano 2014 classification for non-Hodgkin lymphoma) following the most recent systemic therapy;
• At least one bidimensionally measurable lesion, defined as a lesion with the longest dimension \>1.5 cm and perpendicular diameter \>1.0 cm on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), confirmed as positive by PET-CT;
• For DLBCL, prior receipt of at least one line but no more than four lines of systemic therapy, which must include CD20-targeted therapy;
• ECOG performance status score of 0-2.
  • Meet the criteria for autologous hematopoietic stem cell transplantation (ASCT) and be willing to undergo ASCT;
  • Adequate major organ function:
• Liver function: ALT/AST \<3× upper limit of normal (ULN) and total bilirubin ≤34.2 μmol/L;
• Renal function: Creatinine \<220 μmol/L;
• Pulmonary function: Oxygen saturation ≥95% without supplemental oxygen;
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥40%;
• Transplant comorbidity index score ≤3.
  • As judged by the investigator, patients must:
• Be willing to receive adequate prophylaxis and/or treatment for thromboembolic events;
• Be able to understand and sign informed consent, and comply with all study-related procedures, medication use, and evaluations;
• Have no history of non-adherence to medical prescriptions or be deemed by the investigator to have no potential for non-adherence;
• Be able to understand and comply with pregnancy prevention requirements and reasons, the pregnancy prevention risk management plan, and provide written confirmation.