Chimeric antigen receptor T-cell therapy in aggressive lymphomas

Area of Science:

• Hematology
• Oncology
• Immunotherapy

Background:

• Diffuse large B-cell lymphoma (DLBCL) remains a significant challenge in hematologic malignancies.
• Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment modality.

Purpose of the Study:

• To provide an updated review of CAR T-cell therapy in DLBCL as of April 2025.
• To focus on specific patient populations, long-term toxicities, and optimal treatment sequencing.
• To consider the impact of emerging therapies like bispecific antibodies.

Main Methods:

• Review of recent clinical trial data and real-world evidence.
• Analysis of outcomes in specific patient subgroups.
• Evaluation of safety profiles and long-term toxicity data.

Main Results:

• Three CD19-targeting CAR T-cell therapies are approved for third-line DLBCL, achieving up to 40% durable complete remission.
• CAR T-cell therapies are now approved for second-line treatment in refractory or early-relapsed DLBCL.
• Bispecific antibodies offer new options for relapsed/refractory DLBCL, necessitating optimal sequencing strategies.
• Evidence supports CAR T-cell efficacy in elderly patients, transformed indolent B-cell lymphomas, and Richter's transformation.
• Extended follow-up has improved understanding of long-term CAR T-cell therapy toxicities.

Conclusions:

• Recent data enhances understanding of CAR T-cell therapy benefits in specific DLBCL populations.
• Optimization of treatment sequencing and management of long-term toxicities are key areas of focus.
• CAR T-cell therapy continues to evolve as a critical treatment for DLBCL.