Bendamustine-based lymphodepletion prior to CAR T-cell therapy: a systematic review

Area of Science:

• Hematology
• Immunotherapy
• Oncology

Background:

• Lymphodepletion (LD) is crucial for chimeric antigen receptor T-cell (CAR-T) therapy success.
• Fludarabine and cyclophosphamide (Flu/Cy) are the standard LD regimen.
• Bendamustine is an emerging alternative with potential immunomodulatory benefits and a better safety profile.

Purpose of the Study:

• To systematically review the safety, efficacy, and feasibility of bendamustine-based LD in patients undergoing CAR-T therapy for hematologic malignancies.
• To compare bendamustine-based LD with standard Flu/Cy regimens.

Main Methods:

• A comprehensive literature search was performed across major databases and clinical trial registries up to January 2026.
• Included studies reported clinical outcomes of bendamustine-based LD prior to CD19-, CD30-, or BCMA-directed CAR-T therapy.
• Key endpoints included response rates, survival, and treatment-related toxicities.

Main Results:

• Eighteen studies involving over 1400 patients were analyzed.
• Bendamustine-based LD demonstrated comparable efficacy (ORR 50-88%, CRR up to 74%) to Flu/Cy across various hematologic malignancies.
• Significantly lower rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and severe cytopenias were observed with bendamustine.
• Bendamustine facilitated outpatient CAR-T delivery, reducing hospitalizations and ICU stays.
• Prior bendamustine exposure before leukapheresis was linked to poorer CAR-T outcomes.

Conclusions:

• Bendamustine-based LD is a safe and effective alternative to Flu/Cy, especially for outpatient CAR-T therapy and high-risk patients.
• Further prospective, randomized trials are needed to confirm these findings and optimize LD strategies.