Sequential CD19-20 CAR T-cell therapy for refractory/relapsed diffuse large B-cell lymphoma.

Area of Science:

• Immunology
• Oncology
• Hematology

Background:

• Relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) recurrence is often driven by antigen loss and limited CAR T-cell persistence.
• Sequential infusion of CD19 and CD20 CAR T-cells offers a potential strategy to overcome these challenges.

Purpose of the Study:

• To evaluate the safety and efficacy of sequential CD19-20 CAR T-cell therapy in patients with r/r DLBCL.
• To assess the impact of this sequential therapy on response rates and long-term outcomes.

Main Methods:

• A prospective study enrolled 21 patients with r/r DLBCL treated with sequential CD19-20 CAR T-cell therapy.
• Adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were monitored.
• Response rates (partial response - PR, complete response - CR) and duration of response were assessed post-treatment.

Main Results:

• Grade ≥3 CRS occurred in 9.5% of patients; no severe ICANS was observed.
• No treatment-related deaths occurred, and CD20 CAR T-cell infusion did not increase severe toxicity.
• Within 90 days, 61.9% achieved PR and 38.1% achieved CR after CD19 CAR T-cell infusion.
• Sequential CD20 CAR T-cell therapy converted 10 of 13 PR patients to CR.
• At a median follow-up of 24.7 months, 71.4% of patients maintained ongoing responses.

Conclusions:

• Sequential CD19-20 CAR T-cell therapy demonstrates a favorable safety profile in r/r DLBCL.
• This therapeutic approach may enhance long-term clinical outcomes by addressing antigen escape mechanisms.
• Further investigation is warranted to confirm these promising findings.