Daratumumab for CD20^-CD38⁺ Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Area of Science:

• Hematology
• Oncology
• Immunotherapy

Background:

• Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients often exhibit reduced CD20 expression after rituximab treatment.
• Targeted therapy replacement is crucial for R/R DLBCL treatment.
• CD38 expression in R/R DLBCL warrants investigation for alternative therapeutic targets.

Purpose of the Study:

• To evaluate Daratumumab as a monotherapy or combination chemotherapy for CD20-CD38+ R/R DLBCL patients.
• To assess Daratumumab's efficacy in patients who failed prior CD20-targeted treatments.
• To determine Daratumumab's adjuvant effect on subsequent CAR-T (chimeric antigen receptor T-cell immunotherapy).

Main Methods:

• Retrospective analysis of four CD20-CD38+ R/R DLBCL patients treated with Daratumumab-based combination chemotherapy.
• Subsequent CAR-T therapy for eligible patients.
• Construction of allografted tumor models in mice for evaluation.

Main Results:

• Four patients achieved varying remission degrees: 2 complete remissions (CR), 1 partial remission (PR), and 1 stable disease (SD).
• One-year overall survival (OS) rate was 75%, 1-year progression-free survival (PFS) rate was 50%, and median OS (mOS) was 12 months.
• Adverse effects were moderate and reversible; two patients successfully transitioned to CAR-T therapy with manageable grade 1 cytokine release syndrome (CRS).

Conclusions:

• Daratumumab combination therapy shows significant potential for treating CD20-CD38+ R/R DLBCL.
• Daratumumab serves as a viable bridge therapy for subsequent CAR-T treatment.
• This approach offers a promising alternative for R/R DLBCL patients with reduced CD20 expression.