ISSUE: Based on data from two recently halted clinical trials, the U.S. Food and Drug Administration today is issuing this statement to inform the public, health care professionals, and oncology clinical investigators about the risks associated with the use of pembrolizumab (Keytruda) in combination with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) for the treatment of patients with multiple myeloma. Pembrolizumab is not approved for treatment of multiple myeloma.
The FDA statement is based on review of data from two clinical trials (KEYNOTE-183 and KEYNOTE-185) evaluating the use of pembrolizumab combined with other treatments in patients with multiple myeloma. On July 3, 2017, the FDA required that all patients in these trials be discontinued from further investigation with this drug, because interim results from both trials demonstrated an increased risk of death for patients receiving pembrolizumab when it was combined with an immunomodulatory agent as compared to the control group (see statistical analysis section below). Merck & Co., Inc. was made aware of the issue through an external data monitoring committee recommendation and suspended the trials to enrollment on June 12, 2017.
BACKGROUND: This does not apply to patients taking pembrolizumab for an approved indication. Patients on pembrolizumab for an approved use should continue to take their medication as directed by their health care professional.
Pembrolizumab is currently approved by the FDA for treatment of: Melanoma, Lung Cancer, Head and Neck Cancer, Classical Hodgkin Lymphoma, Urothelial Carcinoma, Microsatellite Instability-High (MSI-H) Cancer.
For a summary of the statistical analysis and findings, please refer to the FDA Statement, available at: http://bit.ly/2iJ0du7.
RECOMMENDATION: Other multiple myeloma clinical trials of pembrolizumab, other PD-1/PD-L1 cancer drugs and other combinations are currently undergoing clinical evaluation. The FDA will be working directly with sponsors of pembrolizumab and other PD-1/PD-L1 cancer drugs, as well as clinical investigators conducting clinical trials in patients with multiple myeloma, to determine the extent of the safety issue. The agency will communicate any new information to the public as soon as it is able.
Health care professionals and consumers are encouraged to report any adverse events or side effects related to the use of these products and other similar products to FDA's MedWatch Adverse Event Reporting program:
- Complete and submit the report Online, available at: http://www.fda.gov/MedWatch/report.
- Download form, available at: http://bit.ly/2vMsVvg, or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
Pembrolizumab injection is used to treat several kinds of cancer such as the following: Pembrolizumab injection is in a class of medications called monoclonal antibodies. It works by helping your immune system to slow or stop the growth of cancer cells.
- melanoma (a type of skin cancer) that cannot be treated with surgery or that has spread to other parts of the body;
- a certain type of non-small-cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body (some other types of NSCLC should only be treated with pembrolizumab injection if the cancer has worsened during or after it was treated with other chemotherapy medications);
- a certain type of head and neck cancer that keeps coming back or has spread to other parts of the body that worsened during or after treatment with other chemotherapy medications;
- a certain type of Hodgkin's lymphoma (Hodgkin's disease) in children and adults that did not get better with other chemotherapy treatments or got better but returned after being treated 3 or more times with other chemotherapy medications;
- urothelial cancer (cancer of the lining of the bladder and other parts of the urinary tract) that has spread to nearby tissues or other parts of the body in people who can not receive other types of chemotherapy medications, or whose cancer worsened during or after it was treated with other chemotherapy medications;
- and certain types of colorectal cancer (cancer that begins in the large intestine) and certain types of solid tumors in children and adults that can not be treated by surgery or that has spread to other parts of the body that worsened after it was treated with other chemotherapy medications.
How should this medicine be used?
Pembrolizumab injection comes as a powder to be mixed with liquid and injected intravenously (into a vein) over 30 minutes by a doctor or nurse in a hospital or medical facility. It is usually injected once every 3 weeks for as long as your doctor recommends that you receive treatment.
Pembrolizumab injection may cause serious reactions during, or shortly after the infusion of the medication. If you experience any of the following symptoms, tell your doctor immediately: flushing, fever, chills, shaking, dizziness, feeling faint, shortness of breath, difficulty breathing, itching, rash, or hives.
Your doctor may delay or stop your treatment with pembrolizumab injection, or treat you with additional medications, depending on your response to the medication and any side effects that you experience. Talk to your doctor about how you are feeling during your treatment.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with pembrolizumab injection and each time you receive a dose. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before receiving pembrolizumab injection,
- tell your doctor and pharmacist if you are allergic to pembrolizumab, any other medications, or any of the ingredients in pembrolizumab injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have ever had an organ transplant and if you have or have ever had radiation therapy to your chest area; an autoimmune disease (condition in which the immune system attacks a healthy part of the body) such as Crohn's disease (condition in which the immune system attacks the lining of the digestive tract causing pain, diarrhea, weight loss, and fever), ulcerative colitis (condition which causes swelling and sores in the lining of the colon [large intestine] and rectum), or lupus (condition in which the immune system attacks many tissues and organs including the skin, joints, blood, and kidneys); any type of lung disease or breathing problems; or liver disease.
- tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while you are receiving pembrolizumab injection and for 4 months after you receive your final dose. Talk to your doctor about birth control methods that will work for you. If you become pregnant while receiving pembrolizumab injection, call your doctor immediately. Pembrolizumab injection may harm the fetus.
- tell your doctor if you are breastfeeding or plan to breastfeed. Your doctor may tell you not to breastfeed while receiving pembrolizumab injection, and for 4 months after you receive your final dose.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What side effects can this medication cause?
Pembrolizumab injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- joint or back pain
- swelling of the of the body or face
- changes in skin color
- extreme tiredness or lack of energy
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:
- shortness of breath
- chest pain
- new or worsening cough
- stools that are black, tarry, sticky, or contain blood or mucus
- severe abdominal pain
- severe nausea and vomiting
- increased or decreased appetite
- increased thirst
- pain in the upper right part of the stomach
- yellowing of the skin or eyes
- easy bleeding or bruising
- fast heartbeat
- changes in weight (gain or loss)
- hair loss
- increased sweating
- feeling cold
- deepening of the voice or hoarseness
- swelling in the front of the neck (goiter)
- tingling and weakness in the feet, legs, hands, and arms
- severe or persistent headache, muscle aches
- severe muscle weakness
- dizziness or lightheadedness
- change in the amount or color of urine
- changes in vision
- feeling confused
Pembrolizumab injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to pembrolizumab injection.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.