RETIFANLIMAB-INDUCED THYROID GLAND DYSFUNCTION AND COLITIS (CASE REPORT)
Authors: Kononenko M. G. , Duzhiy I. D. , Moskalenko Y. V. 
Published: July 2023

Immunotherapy is a modern and effective method of treating malignant neoplasms. Retifanlimab is a humanized and stabilized immunoglobulin G4κ monoclonal antibody that binds to PD-1. The drug has been proven to effectively treat cervical cancer and squamous cell tumors of the anal canal caused by the human papillomavirus. Phase III studies of the effectiveness and safety of this monoclonal antibody in patients with non-small cell lung cancer is currently underway.

Patients treated with immunotherapy have an increased risk of developing immune-related adverse events. The most common immune-related side effects in the patient after taking retifanlimab were thyroid gland disorders, itching, pneumonitis and skin rash. In this article, we would like to present a case report of a combined immune-related thyroid and colon dysfunction induced by retifanlimab.

Materials and methods. We collected clinical data and laboratory results of a patient with advanced stage of non-small cell lung cancer. A 59-year-old male patient had disease progression after first-line chemotherapy. He received retifanlimab as second-line therapy at 375 mg intravenously every three weeks.

The results. The first laboratory symptoms of thyroid gland dysfunction began after 36 weeks of taking retifanlimab. After 42 weeks, a laboratory picture of hyperthyroidism was observed with a critically low level of TSH and a high level of T4. In addition, the patient reported diarrhea 7–8 times a day for the last seven days. Immune-related adverse events (colitis grade 3 and hyperthyroidism grade 1) were suspected. The administration of retifanlimab was temporarily discontinued. 750 mg of methylprednisolone was administered once over 60 minutes. The patient's general condition was significantly improved the next day, and prednisolone was prescribed orally at a dose of 2 mg/kg/day. On the second day, diarrhea recurred twice; on the third, the stool returned to normal. Hormone levels were gradually normalized until week 46.

Discussion. Immune-related adverse events may occur as a result of taking any monoclonal antibodies. Early diagnosis and therapy of immune-related adverse reactions is the key to the safe and effective use of PD-1/PD-L1-blocking antibodies.

Immune-related colitis occurred in 1.6% of patients treated with retifanlimab. Hyperthyroidism was observed in 4.3%.

Thyroid disorders that correspond to 1 or 2 grades of severity are common. Therefore patients do not require any medication therapy, or endocrine therapy can be used. However, 13% of patients required systemic corticosteroid therapy. Antihyperthyroidism therapy or corticosteroids (oral prednisolone 1–2 mg/kg/day) are prescribed only when clinical symptoms appear and, accordingly, the severity of the disease is 2 or 3. It is possible to prescribe high-dose steroid therapy.

The appointment of loperamide is sufficient for the initial symptoms of colitis. Therefore, monoclonal antibodies are not discontinued. However, more severe cases require systemic corticosteroids and temporary drug withdrawal. When life-threatening conditions develop, immunotherapy is permanently discontinued.

Conclusions. Immunotherapy is always associated with risk of developing immune-related side effects. Depending on the grade of severity, they require different treatment options. Targeted monitoring of laboratory results and clinical symptoms is the key to safe treatment with immune checkpoint inhibitors.