*Corresponding author:Xiaoli Li Email:fangliaokelixiaoli@163.com
Key Clinical Message: A 65-year-old male patient with lung squamous cell carcinoma, treated with chemotherapy and the PD-1 inhibitor (tirelrelizumab), exhibited abnormal confusion, drowsiness, and other symptoms. After a comprehensive analysis of the clinical manifestations and auxiliary examination, the final diagnosis was immune-mediated encephalitis related to tirellizumab.
Abstract: In the contemporary landscape of oncology, immune checkpoint blockade therapy has emerged as a paramount therapeutic modality. However, concomitant with the pervasive deployment of immune checkpoint inhibitors (ICIs), there has been an escalating incidence of adverse drug reactions over the years.Immunological encephalitis, a prevalent form of central nervous system toxicity, poses a significant threat to the lives of affected patients.A 65-year-old male patient, diagnosed with squamous cell carcinoma of the lung, experienced an atypical immune-mediated encephalitis of clinical nature subsequent to the administration of a PD-1 inhibitor, specifically tirecizumab.The present investigation delved into the clinical presentations and suitable therapeutic protocols for immune-mediated encephalitis.
Keywords:Lung cancer; Tirellizumab; Drug-related adverse reactions; Immune encephalitis
Introduction
Immune checkpoint blockade therapy for PD-1/PD-L1 serves as a breakthrough in the field of antitumor treatment. However, by increasing immune system activity, this therapy can lead to inflammatory side effects, which are often known as immune-related adverse events (irAEs)[1]. In recent years, the increasing use of immune checkpoint inhibitors (ICIs) has led to an annual increase in the incidence of irAEs. Although immune-mediated encephalitis was previously considered rare, a pharmacovigilance study of 48,650 patients with adverse events revealed an incidence of 0.51% for this specific neurotoxicity associated with immune checkpoint inhibitors[2]. Larkin et al. found that immune-mediated encephalitis typically manifests around 55 days after treatment (ranging from 18 to 297 days)[3], with symptoms that are often diverse and atypical.
Case History/examinatian
A 65-year-old male diagnosed with poorly differentiated squamous cell carcinoma of the left hilum in December 2023, with PD-L1 (SP 263) with a tumor cell positive rate of approximately 80%. Due to the ineligibility for a direct surgery, a combination of chemotherapy and immunotherapy was recommended before revaluation. The patient has a medical history of hypertension for 30 years, with a maximum recorded blood pressure of 170/90 mmHg. He is currently taking 1 sustained-release nifedipine tablet daily. He also has a 30-year history of diabetes, with postprandial blood glucose levels reaching as high as 13 mmol/L, for which he has been administering long-acting insulin subcutaneously once a week. In addition, he experienced an old cerebral infarction 2 years ago, for which he did not receive thrombolysis or stent treatment, and continues to have residual neurological symptoms. From January 25, 2024, to February 25, 2024, the patient underwent 2 cycles of chemotherapy combined with immunotherapy. The treatment regimen included paclitaxel (albumin-bound type 260 mg/m2) 400 mg on days 1 and 8, along with carboplatin (AUC=5-7) at 400 mg on day 1, administered every 21 days, in combination with immunization (tirelizumab 200 mg every 21 days).
On the morning of March 8, 2024, the patient had sudden confusion, poor speech, drowsiness, and other manifestations. The physical examination was uncooperative. An emergency CT scan was performed upon admission, revealing the following findings: (1) Possible ischemic infarctions in the bilateral lateral ventricles, left basal ganglia, and brainstem; and (2) swelling of the left top subcutaneous soft tissue. Brain diffusion-weighted imaging (DWI) indicates abnormal signals in the left thalamus and pons, suggesting an old cavity infarction. The patient’s main blood biochemistry upon admission was as follows: (1) Blood cell analysis: white blood cell count: 10.8 * 10^9/L; red blood cell count: 3.31 * 10^12/L; hemoglobin: 99.0 g/L; platelet count: 256.0 * 10^9/L; platelet ocrit: 0.201%; neutrophil percentage: 86.6%; absolute neutrophil value: 9.4 * 10^9/L; hypersensitivity C-reactive protein: 95.68 mg/L. (2) Liver function: alanine aminotransferase: 15.7 U/L; aspartate aminotransferase: 16.5 U/L; albumin: 37.4 g/L; total bilirubin: 10.09 μmol/L; direct bilirubin: 4.25 μmol/L; indirect bilirubin: 5.84 μmol/L; alkaline phosphatase: 65.1 U/L; r-glutamyltransferase: 17.7 U/L; (3) Serum electrolytes: sodium: 130.8 mmol/L; and (4) Arterial blood gas analysis: lactic acid: 0.5 mmol/L; Negative log of hydrogenion concmtra ion: 7.28; Partial pressure of carbon dioxide: 35.50 mmHg; actual bicarbonate: 16.20 mmol/L; standard bicarbonate: 16.40 mmol/L; anion gap: 19.20 mmol/L; residual base: 9.40 mmol/L; arterial blood oxygen partial pressure 35.00 mmHg; blood oxygen saturation: 67.20%; arterial blood oxygen content: 2.66 mmol/L; hemoglobin concentration: 62.00 g/dL; oxygen partial pressure in the alveoli and arteries: 53.00 mmHg; and potassium: 4.71 mmol/L.