*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.