(PO-018) (PO-018) Pembrolizumab-induced autoimmune encephalitis: A Case Report and Discussion

Background: Over the past decade, immune checkpoint inhibitors (ICPis) have revolutionized the treatment of advanced lung cancers. Among them anti-programmed cell death protein 1 (PD-1) and programmed-death ligand 1 (PD-L1) inhibitors have demonstrated remarkable clinical responses with improvement in overall survival in patients with advanced non-small cell lung cancer (NSCLC). As such, anti-PD-1 inhibitors like Pembrolizumab are now considered first-line treatments for patients with PD-L1-positive tumors.⁽¹⁾ However, ICPis may be associated with immune-related adverse events, including autoimmune encephalitis (AIE), which is rare but a potentially fatal complication.⁽²⁾

Methods: We present a case of a 61-year-old white male diagnosed in May 2019 with widely metastatic stage IVB NSCLC complicated by cerebral vasogenic edema requiring urgent whole brain radiation therapy. He was subsequently treated with three cycles systemic chemotherapy plus pembrolizumab and then continued on maintenance therapy with pemetrexed and pembrolizumab from October 2019 to November 2020, then pembrolizumab monotherapy until January 2021 when he was hospitalized following a rapid global decline in mental status with workup non-revealing for other causes. A clinical diagnosis of autoimmune encephalitis was made and he was empirically initiated on high dose IV corticosteroids with significant improvement over the course of the next two weeks.

Discussion: Our literature search revealed only a few published case reports of autoimmune encephalitis in patients with lung cancer following anti-PD 1 inhibitor therapy. Immune checkpoints function to maintain self-tolerance and prevent autoimmunity. Due to their unique mechanism of action, ICPIs may be associated with immune-related adverse events although fortunately neurologic complications like AIE occur in less than 1% of patients. Given the limitations of current research, the exact etiology of AIE remains unclear. The diagnosis of AIE can be challenging and is largely based on clinical history and presentation. Management includes cessation of anti-PD-1 inhibitor therapy and initiation of immunosuppressive therapy including corticosteroids plasma exchange, IVIG, and/or tumor necrosis factor-alpha (TNF-a) inhibitors. Responses to treatment appear to vary and not all patients will have a meaningful recovery.^(2),(3)

Conclusions: While autoimmune encephalitis following anti-PD-1 inhibitor therapy is rare, prompt recognition and initiation of treatment can be life-saving. As anti-PD-1 inhibitors are becoming standard therapy for an increasing number of oncologic diseases, the consult-psychiatrist should be familiar with its clinical presentation. Clearly, more research is needed to help clarify diagnostic criteria and optimal management guidelines.

References:

Rihawi et al. Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of the current evidence. 2017.

Niki et al. Pembrolizumab-induced autoimmune encephalitis in a patient with advanced non-small cell lung cancer: A case report. 2019.

Shah et al. Nivolumab-induced autoimmune encephalitis in two patients with lung adenocarcinoma. 2018.

Vogrig et al. Central nervous system complications associated with immune checkpoint inhibitors. 2020.

Learning Objectives:
Describe the unique mechanism of action of immune checkpoint inhibitors (ICPis) that can lead to immune related adverse effects.
Summarize the clinical presentation of autoimmune encephalitis following anti-PD-1 inhibitor therapy.
Identify strategies for diagnosis and management of autoimmune encephalitis following anti-PD-1 inhibitor therapy

Presenting Author(s)

Maher Almatrafi, MBBS
– Geriatric Psychiatry Fellow, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
Co-Author(s)

Katy LaLone, MD
– Assistant Professor of Psychiatry, Case Western Reserve University - University Hospitals, Cleveland, OH, United States