Toxicities Associated with CAR-T Cell Therapies

Area of Science:

• Immunology
• Oncology
• Cellular Therapy

Background:

• Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for relapsed/refractory B-cell malignancies.
• Despite efficacy, CAR-T therapy presents significant toxicities impacting patient morbidity and mortality.

Purpose of the Study:

• To review and clarify the distinct toxicities associated with CAR-T cell therapy.
• To elucidate the mechanisms underlying these adverse events.

Main Methods:

• Literature review of studies defining CAR-T cell therapy toxicities.
• Analysis of reported mechanisms for acute and late-onset toxicities.

Main Results:

• Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are primary acute toxicities.
• Late toxicities include B-cell aplasia, hypogammaglobulinemia, infections, and cytopenias.
• Infections are the leading cause of non-relapse mortality; secondary myeloid malignancies are rare.

Conclusions:

• CAR-T therapy requires careful toxicity monitoring and management strategies.
• Further research into mitigating these adverse events is essential for broader CAR-T application.