Severe Neuromyelitis Optica Spectrum Disorder Triggered by Pucotenlimab: Case Report

Overview

A patient with advanced triple-negative breast cancer developed severe neuromyelitis optica spectrum disorder (NMOSD) after treatment with the immune checkpoint inhibitor pucotenlimab. Despite aggressive immunosuppressive therapy, the patient's neurological condition deteriorated, culminating in multiple organ dysfunction and death.

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can cause immune-related adverse events (irAEs), including rare but severe neurological irAEs (N-irAEs). Neurological irAEs have a higher mortality rate and are often refractory to corticosteroids, necessitating prompt diagnosis and management. Pucotenlimab, a PD-1 inhibitor, is used as salvage therapy in metastatic triple-negative breast cancer but may trigger severe autoimmune complications such as NMOSD.

Data Highlights

The patient was a 56-year-old female with stage IV triple-negative invasive ductal breast carcinoma. After salvage therapy initiation with eribulin plus pucotenlimab, neurological symptoms developed within approximately two weeks. Despite high-dose methylprednisolone and plasma exchange, neurological symptoms worsened, leading to multiple organ dysfunction syndrome and death.

Key Findings

• Neurological immune-related adverse events (N-irAEs) are rare but have high mortality and can be triggered by ICIs like pucotenlimab.
• The patient developed anti-aquaporin 4 antibody (AQP4-Ab)-positive NMOSD following pucotenlimab treatment.
• High-grade N-irAEs often do not respond to first-line corticosteroid therapy and require timely second-line interventions.
• Despite prompt immunosuppressive treatment, the patient’s neurological symptoms progressed, resulting in fatal multiple organ dysfunction.
• Diagnosis of N-irAEs is challenging due to nonspecific symptoms and requires multidisciplinary evaluation.

Clinical Implications

Clinicians should maintain high suspicion for severe neurological irAEs such as NMOSD in patients receiving ICIs like pucotenlimab. Early multidisciplinary diagnosis and aggressive immunosuppressive therapy are critical, although some cases may remain refractory. Awareness of this potential fatal complication is essential for timely intervention and patient counseling.

Conclusion

This case highlights the potential for severe, life-threatening NMOSD triggered by pucotenlimab in cancer patients. Vigilant monitoring and rapid management of neurological symptoms are imperative to improve outcomes in ICI-treated patients.

References

1. Case Study and Literature Analysis, 2024 -- Severe Neuromyelitis Optica Spectrum Disorder Triggered by Pucotenlimab