Decitabine-primed tandem CD19/CD22 CAR-T therapy in relapsed/refractory diffuse large B-cell lymphoma patients

Area of Science:

• Oncology
• Immunotherapy
• Hematology

Background:

• Relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) has limited treatment options.
• Current CAR-T therapy achieves sustained responses in only about 40% of patients.

Purpose of the Study:

• To evaluate the efficacy and toxicity of tandem CD19-CD22 CAR-T cells combined with decitabine-based lymphodepletion chemotherapy in R/R DLBCL patients.
• To identify prognostic factors for survival outcomes in this patient population.

Main Methods:

• A phase II clinical trial (NCT03196830) enrolled R/R DLBCL patients.
• Patients received decitabine, fludarabine, and cyclophosphamide (DFC) lymphodepletion chemotherapy followed by CD19-CD22 CAR-T cell infusion.
• Efficacy and toxicities were assessed with a median follow-up of 10.9 months.

Main Results:

• The overall response rate was 90.9%, with a complete remission (CR) rate of 63.6%.
• Median progression-free survival (PFS) was 10.2 months, and 2-year PFS was 47.2%.
• No severe grade 4 cytokine release syndrome (CRS) occurred; toxicities were transient and reversible, with no CAR-T-related mortality.

Conclusions:

• CD19/CD22 dual-targeted CAR-T therapy with decitabine-containing lymphodepletion is a safe and potent approach for R/R DLBCL.
• Achieving CR and avoiding severe CRS were independent prognostic factors for improved PFS and overall survival (OS).