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

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, Prospective Phase II Clinical Study

This study aims to evaluate the efficacy and safety of tafasitamab combined with lenalidomide plus standard immunochemotherapy, followed by sequential autologous stem cell transplantation (ASCT), in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Inclusion Criteria

Age ≥18 years;

Pathologically confirmed diagnosis of relapsed or refractory DLBCL;

Patients must meet the following criteria:

1. 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;
2. 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;
3. For DLBCL, prior receipt of at least one line but no more than four lines of systemic therapy, which must include CD20-targeted therapy;
4. 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:

1. Liver function: ALT/AST <3× upper limit of normal (ULN) and total bilirubin ≤34.2 μmol/L;
2. Renal function: Creatinine <220 μmol/L;
3. Pulmonary function: Oxygen saturation ≥95% without supplemental oxygen;
4. Cardiac function: Left ventricular ejection fraction (LVEF) ≥40%;
5. Transplant comorbidity index score ≤3.

As judged by the investigator, patients must:

1. Be willing to receive adequate prophylaxis and/or treatment for thromboembolic events;
2. Be able to understand and sign informed consent, and comply with all study-related procedures, medication use, and evaluations;
3. Have no history of non-adherence to medical prescriptions or be deemed by the investigator to have no potential for non-adherence;
4. Be able to understand and comply with pregnancy prevention requirements and reasons, the pregnancy prevention risk management plan, and provide written confirmation.

Exclusion Criteria

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

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;

Uncontrolled infectious disease within 4 weeks prior to enrollment;

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;

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);

Psychiatric illness;

Substance abuse/dependence;

Any other condition that, in the investigator's judgment, makes the patient unsuitable for enrollment.