Neurologic Toxicities of Immunotherapy

Area of Science:

• Oncology
• Immunology
• Neuroscience

Background:

• Immunotherapy has transformed cancer treatment, but immune-related adverse events (irAEs) arise from on-target, off-tumor effects.
• Neurological irAEs, though rare with immune checkpoint inhibitors (CPIs), present diverse phenotypes and management challenges.
• Immune effector cell-associated neurotoxicity (ICANS) is frequent, often co-occurring with cytokine release syndrome (CRS), impacting therapy development.

Purpose of the Study:

• To describe the clinical phenotypes of CPI-induced neurological complications.
• To outline the clinical phenotypes of immune effector cell-associated neurotoxicity (ICANS).
• To discuss strategies for clinical monitoring, diagnosis, and management of these neurological syndromes.

Main Methods:

• Review of clinical phenotypes associated with CPI-induced neurological complications.
• Review of clinical phenotypes associated with ICANS.
• Discussion of clinical monitoring, diagnostic approaches, and management strategies.

Main Results:

• CPI-induced neurological complications exhibit heterogeneous clinical presentations.
• ICANS is a common neurotoxicity associated with immune effector cell therapies, often linked to CRS.
• Effective management requires early recognition, timely diagnosis, and tailored interventions.

Conclusions:

• Neurological irAEs and ICANS are significant challenges in cancer immunotherapy.
• Understanding diverse clinical phenotypes is essential for prompt diagnosis and intervention.
• Strategic monitoring and management are critical for advancing the clinical development of immunotherapies.