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Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment
Justine V Cohen1, Ahmed K Alomari2, Alexander O Vortmeyer2
1Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut.
Abstract:
The role of immunotherapy in treatment of brain metastases is unknown because most trials exclude patients with active brain lesions. As new immunomodulating agents gain approval for many malignancies, it is important to know if they have unique effects in the central nervous system (CNS). Here, we present a case of a patient with progressing brain metastases treated with a single cycle of pembrolizumab, who presented with mental status changes 11 days thereafter. MRI of the brain showed enlargement of CNS lesions with intense central enhancement and diffuse perilesional edema. Histologic evaluation of a resected lesion revealed isolated clusters of tumor cells surrounded by reactive astrocytosis, scattered inflammatory cells, and an abundance of microglial cells. Given the increasing use of immune checkpoint inhibitors in patients with brain metastases from melanoma and other diseases, recognition of pseudoprogression and management with immune suppression are essential.
Insights
Immunotherapy can cause pseudoprogression in brain metastases, mimicking tumor growth. Recognizing this immune-related adverse event is crucial for managing patients receiving immune checkpoint inhibitors.
Area of Science:
- Neuro-oncology
- Immunology
- Radiology
Background:
- The efficacy of immunotherapy for brain metastases is largely unknown due to trial exclusions of patients with active central nervous system (CNS) lesions.
- The increasing use of immunomodulating agents necessitates understanding their specific effects within the CNS.
Observation:
- A patient with progressing brain metastases experienced altered mental status 11 days after a single cycle of pembrolizumab.
- Brain MRI revealed enlarged CNS lesions with central enhancement and significant perilesional edema, suggestive of progression.
Findings:
- Histological examination of a resected lesion showed tumor cells amidst reactive astrocytosis, inflammatory cells, and abundant microglia.
- These findings are consistent with an immune-mediated response rather than true tumor progression.
Implications:
- Pseudoprogression, an immune-related adverse event, can mimic tumor growth in brain metastases treated with immunotherapy.
- Distinguishing pseudoprogression from true progression is essential for appropriate patient management, potentially involving immune suppression.
- This case highlights the importance of considering immune-related effects in patients with brain metastases receiving immune checkpoint inhibitors.
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