How I treat refractory/relapsed diffuse large B-cell lymphomas with CD19-directed chimeric antigen receptor T cells

Area of Science:

• Hematology
• Immunotherapy
• Oncology

Background:

• Chimeric antigen receptor (CAR) T cells targeting CD19 are a key salvage immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).
• Clinical practice involves complex cases and therapeutic decisions for R/R DLBCL patients undergoing CAR T-cell therapy.
• Understanding CAR T-cell failure mechanisms is crucial for optimizing treatment strategies.

Purpose of the Study:

• To provide criteria and new perspectives for CAR T-cell treatment of DLBCL.
• To address challenges in selecting bridging therapy and managing post-CAR T-cell therapy relapses.
• To discuss diagnostic complexities and therapeutic choices in R/R DLBCL management.

Main Methods:

• Review of current literature and clinical practices in CAR T-cell therapy for DLBCL.
• Presentation of four instructive cases illustrating diagnostic and therapeutic challenges.
• Discussion of advances in understanding CAR T-cell failure mechanisms.

Main Results:

• CAR T-cell therapy achieves long-term responses in approximately 40% of R/R DLBCL patients.
• Positron emission tomography/computerised tomography may lead to false-positive interpretations, underscoring the need for post-treatment biopsy.
• Novel immunotherapeutic agents and insights into CAR T-cell failure necessitate a rational treatment approach.

Conclusions:

• A rational approach is needed to select bridging therapy and manage relapses in R/R DLBCL patients treated with CAR T cells.
• Accurate diagnosis, including post-treatment biopsy, is essential for effective management.
• This review offers criteria and new perspectives to guide CAR T-cell treatment decisions in DLBCL.