Unexpected Adverse Events of Immune Checkpoint Inhibitors

Abstract

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter's syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis.

Keywords: Reiter’s syndrome; autonomic neuropathy; immune checkpoint inhibitors; immune related adverse events; myasthenia gravis; palmoplantar keratoderma; pembrolizumab.

Figure 1

MRI of the head revealed no pathologic findings or evidence of metastasis.

Figure 2

Palmoplantar keratoderma of hands and feet observed prior to discontinuing pembrolizumab and initiating dermatological treatment.

Figure 3

Palmoplantar keratoderma improvement after stopping pembrolizumab and using the dermatological treatment.

Figure 4

During dermatological therapy, a notable improvement in palmoplantar keratoderma on the hands and feet was observed.

Figure 5

Patient at presentation, showing bilateral ptosis (drooping of the eyelids) along with near-complete ophthalmoplegia (paralysis or weakness of eye movements).

Figure 6

Depicts the patient after undergoing corticosteroid therapy with prednisone at a dose of 1 mg/kg for a period of two weeks.

Figure 7

Depicts the patient’s condition, and an improvement of bilateral ptosis following the 2nd day of IV.IG.

Figure 8

Depicts the patient’s condition, and the improvement of bilateral ptosis immediately after IV-IG therapy.