Pembrolizumab (brand name: Keytruda) is a type of injected immunotherapy medicine used to treat many different types of cancer. Immunotherapy can sometimes cause your immune system to attack healthy organs and tissues and lead to side effects. These side effects may be serious or life-threatening. This may happen anytime during or after treatment.

Many of these reactions are uncommon or rare, but talk to your doctor to better understand your expected outcomes with immunotherapy treatment.

Immune-mediated side effects can affect your:

• lungs
• intestine
• liver
• hormone glands (especially the thyroid, pituitary, adrenal glands, and pancreas)
• kidney
• skin
• other organs

Ask your doctor or pharmacist for the Medication Guide, which has a listing of side effects that may occur if your immune system is affected by pembrolizumab. Also ask how often these effects may occur in patients with your cancer type. Rates of side effects due to immune-mediated effects may be different based on the type of cancer being treated.

If these symptoms occur, you may need to stop treatment temporarily or permanently and receive other treatments such as corticosteroids (“steroids” like prednisone) or hormone replacement therapy. Contact your doctor immediately if you experience any of these side effects to help keep them from becoming more serious.

Examples of types of cancers that pembrolizumab treats include: melanoma (advanced skin cancer), lung cancer, lymphoma (blood cancer), bladder cancer, kidney cancer, stomach cancer and some forms of breast cancer, but it treats may other types.

How often do immune system problems occur with pembrolizumab?

Cancer treatment is always individual, and what you experience may be different from someone else.

In clinical studies, researchers looked at a large group of patients to better understand how frequently and how quickly these side effects might occur, but these numbers have a wide range.

Your outcome may be different based on your cancer type, overall medical condition, other treatments you are receiving, and many other factors. Always discuss the potential for drug side effects with your doctor, who knows your medical history and treatment plan best.

Lung problems (pneumonitis, swelling in your lungs):

• shortness of breath
• chest pain
• new or worsening cough

In studies with pembrolizumab used for various cancers, pneumonitis occurred in 94 of 2799 (3.4%, or 3.4 out of every 100) of patients. These side effects most commonly started 3.3 months after beginning treatment, but ranged between 2 days and 19.3 months. They lasted 1.5 months (range: 1 day to over 17.2 months). Pneumonitis was resolved in 55 out of the 94 patients (59%) and 36 patients (1.3%) had to stop treatment.

Intestinal problems (colitis) can lead to tears or holes in your intestine. Signs and symptoms of colitis may include:

• diarrhea or more frequent bowel movements
• stools that are black, tarry, sticky, or contain blood or mucus
• severe pain or tenderness in the stomach area (abdomen)

Colitis occurred in 48 of 2799 (1.7%) of patients receiving pembrolizumab, and started most commonly in 3.5 months (range: 10 days to 16.2 months). Symptoms most commonly lasted about 1.3 months (range: 1 day to over 8.7 months). Colitis was resolved in 41 out of the 48 patients (85%) but 15 patients (0.5%) had to stop treatment.

Liver problems that may include hepatitis (inflammation of the liver):

• yellowing of your skin or the whites of your eyes
• nausea or vomiting
• pain on the right side of your stomach area (abdomen)
• dark urine
• bleeding or bruising more easily than normal

In studies, liver problems like hepatitis occurred in 19 of 2799 (0.7%) patients receiving pembrolizumab. It occurred most commonly at 1.3 months (range: 8 days to 21.4 months). Symptoms most commonly lasted about 1.8 months (range: 8 days to over 20.9 months). Hepatitis was resolved in 15 out of the 19 patients (79%) but 6 patients (0.2%) had to stop treatment.

Hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas): signs or symptoms that you may be having a problem with your hormone glands include:

• rapid heart beat
• weight loss or weight gain
• increased sweating
• feeling more hungry or thirsty
• urinating more often than usual
• hair loss
• feeling cold
• constipation
• your voice gets deeper
• muscle aches
• feeling very weak, dizziness or fainting
• headaches that will not go away or unusual headache

Adrenal insufficiency: The adrenal glands are located on top of each kidney and secretes important hormones, including sex hormones and cortisol. In studies, adrenal insufficiency occurred in 22 of 2799 (0.8%) of patients. Onset of adrenal insufficiency occurred in 5.3 months most commonly (range: 26 days to 16.6 months), but the length of time it lasted ranged from 4 days to longer than 1.9 years. Pembrolizumab treatment was stopped in less than 0.1% of patients due to this effect, and doses were withheld in 0.3% of patients.

Pituitary gland problems (hypophysitis) occurred in 17 of 2799 (0.6%) patients receiving pembrolizumab. It occurred most commonly at 3.7 months (range: 1 day to 11.9 months). Symptoms most commonly lasted about 4.7 months (range: 8 days to over 12.7 months). Hypophysitis was resolved in 7 out of the 17 patients (41%) but 4 patients (0.1%) had to stop treatment.

Thyroid gland disorders: Pembrolizumab can also cause thyroid disorders. Your doctor will monitor you periodically for changes in your thyroid.

• Hyperthyroidism occurred in 96 (3.4%) of 2799 patients and most commonly occurred in 1.4 months (range: 1 day to 21.9 months)
• Hypothyroidism occurred in 237 (8.5%) of 2799 patients and most commonly occurred in 3.5 months (range: 1 day to 18.9 months)
• Thyroiditis occurred in 16 (0.6%) of 2799 patients and most commonly occurred in 1.2 months (range: 0.5 to 3.5 months).

Type 1 diabetes mellitus, including diabetic ketoacidosis, has been reported in 6 of 2799 (0.2%) of patients receiving pembrolizumab. Your doctor should monitor you for high blood sugar (hyperglycemia) and other symptoms of diabetes.

Kidney problems (immune-mediated nephritis and renal dysfunction): Your doctor will monitor your kidney function closely. Signs and symptoms of kidney problems may include:

• a change in the amount or color of your urine

Nephritis occurred in 9 of 2799 patients (0.3%) receiving pembrolizumab. Nephritis was resolved in 5 out of the 9 patients (56%) but 3 patients (0.1%) had to stop treatment.

Skin Reactions: Serious or fatal skin reactions can occur with pembrolizumab. Signs of skin problems include:

• a rash
• itching
• blisters, peeling or skin sores
• painful sores or ulcers in your mouth or in your nose, throat, or genital area

Other immune-mediated side effects, which may be severe or fatal, can occur in any organ system or tissue, usually while you are receiving pembrolizumab. But side effects can occur after your treatment has stopped, too. Signs and symptoms of these problems may include:

• changes in eyesight
• severe or persistent muscle or joint pains
• severe muscle weakness
• low red blood cells (anemia)
• swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis)
• confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, or seizures (encephalitis)
• pain, numbness, tingling, or weakness in your arms or legs, or bladder or bowel problems, including the need to urinate more often, leaking of urine, trouble urinating, or constipation (myelitis)
• shortness of breath, irregular heartbeat, feeling tired, or chest pain (myocarditis)

Pembrolizumab can also cause immune problems that lead to solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation, meaning you would receive stem cells from a healthy person (the donor).

Bottom Line

• Pembrolizumab (brand name: Keytruda) is an injected immunotherapy drug used to treat various types of cancer.
• Immunotherapy may cause your immune system to attack healthy organs and tissues and lead to side effects that may be severe or fatal. Immune-mediated reactions may occur anytime during or after treatment with pembrolizumab.
• Many of these reactions are uncommon or rare, but talk to your doctor to better understand your expected outcomes with immunotherapy treatment.

This is not all the information you need to know about pembrolizumab (brand name: Keytruda) for safe and effective use. Review the full pembrolizumab product information here, and discuss this information with your doctor or other health care provider.