Check Point Inhibitor Side Effects
Check point inhibitors: cytotoxic T lymphocyte associated protein 4 (CTLA 4) inhibitors and programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL1) have changed the way we practice oncology.
In general check point inhibitors are well tolerated and the majority of patients will have no side effects.
Having said that, attention must be paid when side effects occur because they are auto immune and can be potentially severe.
The CTLA-4 inhibitor can have severe reactions ranging between 10-30% while PDL1 and PD1 inhibitors can have severe reactions between 5-20%.
The most common endocrine dysfunction is hypothyroidism and hypophysitis. Diabetes, adrenal insufficiency and hyperthyroidism occur rarely.
Hypothyroidism occurs 5-10% of the time. It presents first as thyrotoxicosis, followed by decreased thyroid function. Patient’s symptoms and thyroid function, including T3, T4 and TSH, have to be monitored.
Hypophysitis grade three or four can happen >10% of the time with CTLA – four inhibitors and 1% with PDL1, PD1 inhibitors. The most common side effects with hypophysitis are fatigue and frequent H/A. The biggest problem with hypophysitis is acquired deficiency of anterior pituitary hormones and in particular the adrenocorticotropic hormone (ACTH) leading to adrenal insufficiency and lack of secretion of cortisol. Lack of cortisol cases syncope and hypotension which can be life threatening if not treated promptly.
The patients need to be monitored closely with labs every four weeks. If signs of endocrine dysfunction emerge the patient needs to be seen and followed by an endocrinologist.
If symptoms of hypophysitis are severe, ACT H and Cortisol need to be checked and the patient needs to be promptly treated with steroids.
If the patient presents with headaches, an MRI of the brain to assess the pituitary gland needs to be obtained.
Patients need to be monitored closely and a high index of suspicion is needed.
All patients who develop endocrinopathy will need to be followed by an endocrinologist regardless of the severity of the disease.
Type 1 diabetes is much more rare than thyroid dysfunction. It occurs less than 1% of the time but the patient can present with ketoacidosis, which requires hospitalization. Therefore, close monitoring of the patient and labs is needed.