Immune-Related Adverse Events in a Patient Treated with Pembrolizumab: A Case Report from the Point of View of a Geriatrician

Abstract

We report the case of a 78-year-old female patient who received palliative immunotherapy with pembrolizumab and lenvatinib as a treatment of pulmonary and osseous metastatic endometrial carcinoma. Under this therapy, the patient developed dysphagia, thyroiditis with hypothyroidism, myositis, and myocarditis, which required, due to third-degree AV block, the installation of a pacemaker. The patient received high-dose cortisone therapy, a thyroid hormone substitution, and pyridostigmine for symptom control. With this therapy, we saw a significant but not complete regression of symptoms. Ultimately, we could discharge the patient home for an outpatient treatment. The case report is followed by a discussion of the management of immune-related adverse events (irAEs) during pembrolizumab therapy from a geriatric perspective. Elderly patients on pembrolizumab therapy require close monitoring for irAEs, which can present atypically or without symptoms and may be fatal. Non-invasive diagnostics and minimizing hospital stays are essential to preserve the fitness of this vulnerable population.

Keywords: geriatrics; immune checkpoint inhibitor; immune myocarditis; immune-related adverse events; pembrolizumab; third-degree atrioventricular block.

Figure 1

Overview of the time sequence before hospitalization, the performed diagnostics, and important events during hospitalization; blood draws are marked with a red drop below the timeline; additionally marked in blue are the doses of prednisolone therapy. CT: computer tomography; PM: pacemaker.

Figure 2

Changes in Electrocardiography. (A) The 12-lead ECG at admission: third-degree AV block with a heart rate of 52 bpm and over-rotated left type; The atrial rhythm with a regular P-to-P interval; marked in red. The escape rhythm with a regular R-to-R interval; marked in blue, which is interrupted by numerous ventricular extrasystoles; marked in green. (B) The 12-lead ECG dated 5 months before: a regular sinus rhythm with a heart rate of 76 bpm; indifference type; regular R wave transition between V 3 and V 4.

Figure 3

The time course of measured laboratory parameters. Day 0 is defined as the day of hospital admission; day 16 as the day of discharge; the start of therapy on day 9; dashed lines each mark the border of the reference range (RR). (A) cTnT as a parameter for the course of myocarditis after the start of therapy (RR = 0.014 ng/mL). (B) Creatine kinase as a course parameter for myositis (RR = 170 U/l). (C) The time course of thyroiditis and associated hypothyroidism with TSH (black, left scale, RR = 4.2 μIU/mL) and T3 (blue, right scale, RR = 2.0 pg/mL). cTnT, cardiac troponin T; RR, reference range; TSH, thyroid-stimulating hormone; T3, triiodothyronine.

Figure 4

Clinical course of ptosis under glucocorticoid therapy; on the day of initiation of therapy (A), the day after initiation of therapy (B), and 3 days after initiation of therapy (C). Reproduced with permission of the patient.