FDA is alerting patients and health care professionals that a clinical trial (OCEAN, Study OP-103) evaluating Pepaxto (melphalan flufenamide) with dexamethasone to treat patients with multiple myeloma showed an increased risk of death.
The trial compared Pepaxto with low-dose dexamethasone to pomalidomide with low-dose dexamethasone in patients with relapsed or refractory (resistant) multiple myeloma following 2-4 lines of prior therapy and in patients who were resistant to lenalidomide in the last line of therapy.
FDA encourages health care professionals to review patients' progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments. Patients currently receiving Pepaxto should also discuss with their health care professional the risks and benefits of receiving Pepaxto.
In February 2021, FDA approved Pepaxto under Accelerated Approval for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. The manufacturer, Oncopeptides AB, was required to conduct the OCEAN trial as a post-approval requirement under the accelerated approval program.
Due to the detrimental effect on overall survival in the OCEAN trial, FDA is requiring the manufacturer suspend enrollment in the trial. FDA has also suspended enrollment in other ongoing Pepaxto clinical trials. Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.
FDA continues to evaluate the OCEAN trial results and may hold a future public meeting to discuss these safety findings and explore the continued marketing of Pepaxto. The agency will update patients and health care professionals when new information is available.
Why is this medication prescribed?
Melphalan flufenamide injection is used along with dexamethasone to treat multiple myeloma (a type of cancer of the bone marrow) in adults whose disease has returned or has not improved after receiving at least four other chemotherapy medications. Melphalan flufenamide is in a class of medications called alkylating agents. It works by stopping or slowing the growth of cancer cells in your body.
How should this medicine be used?
Melphalan flufenamide injection comes as a powder to be mixed with liquid to be slowly injected intravenously (into a vein) over 30 minutes by a doctor or nurse in a medical facility. It is usually given once every 4 weeks. The length of treatment depends on how well your body responds to treatment.
Your doctor may need to delay your treatment or adjust your dose if you experience certain side effects. It is important for you to tell your doctor how you are feeling during your treatment with melphalan flufenamide.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
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 melphalan flufenamide injection,
- tell your doctor and pharmacist if you are allergic to melphalan flufenamide, melphalan, any other medications, or any of the ingredients in melphalan flufenamide injection. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
- tell your doctor if you have a infection.
- you should know that melphalan flufenamide may interfere with the normal menstrual cycle (period) in women and may temporarily or permanently stop sperm production in men. Melphalan flufenamide may cause infertility (difficulty becoming pregnant); however, you should not assume that you cannot get pregnant or that you cannot get someone else pregnant. Tell your doctor if you are pregnant or plan to become pregnant. You will need to have a pregnancy test before you start treatment with melphalan flufenamide. If you are female, you should use birth control to prevent pregnancy during your treatment and for 6 months after you stop receiving melphalan flufenamide injection. If you are male, you and your female partner should use birth control during your treatment and for 3 months after you stop receiving melphalan flufenamide injection. If you become pregnant while using receiving melphalan flufenamide injection, call your doctor. Melphalan flufenamide may harm the fetus.
- Tell your doctor if you are breastfeeding. You should not breastfeed during your treatment with melphalan flufenamide and for 7 days after your final dose.
What side effects can this medication cause?
Melphalan flufenamide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- decreased appetite
- joint, muscle or back pain
- difficulty falling asleep or staying asleep
- swelling of the face, arms, hands, feet, ankles or lower legs
Some side effects can be serious. If you experience any of these symptoms call your doctor immediately or get emergency medical treatment:
- fever, sore throat, ongoing cough and congestion, or other signs of infection
- frequent, painful, or burning feeling during urination
- unusual bleeding or bruising
- bloody or black, tarry stools
- bloody vomit or vomiting blood or brown material that resembles coffee grounds
- pale skin
- unusual tiredness or weakness
- shortness of breath
- dizziness, lightheadedness, or fainting
- fast, irregular, or pounding heartbeat
Melphalan flufenamide may increase the risk that you will develop other cancers. Talk to your doctor about the risks of taking this medication.
Melphalan flufenamide may cause other side effects. Call your doctor if you have any unusual problems while taking 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 the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call 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 melphalan flufenamide.
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.
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