Overview
Daratumumab was first approved by the food drug administration in November 2015 as a monotherapy for patients with multiple myeloma. It was later approved in 2016 to be used in conjugation with other drugs like Lenalidomide for the treatment of multiple myeloma. It is targeted immunotherapy and contains monoclonal antibodies. It helps to boost the immune system against infections. The approval was based entirely on two randomized, open-label trials in which the drug was introduced to the standard therapies.
Ever since, the drug has been the first choice of treatment in multiple myeloma, a bone marrow cancer. It has helped benefit various individuals who had unsuccessful chemotherapy treatment for a while. Daratumumab is an immunotherapeutic drug that contains antibodies to fight against infection and boost immunity.
How Does Daratumumab Work?
Daratumumab is a drug used specifically to treat multiple myeloma, cancer affecting white blood cells. It acts by blocking a specific protein in the body that is responsible for tumor cell growth. This drug helps protect healthy cells from further damage. It binds to CD38, causing cell death or apoptosis. This process is mediated with the help of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.
Uses of Daratumumab:
Multiple Myeloma
A form of cancer that affects plasma cells, a type of white blood cell. It is also called a bone marrow tumor. The immunity of the affected individual is highly compromised. The drug helps to boost immunity by eliminating the affected cells and protecting the healthy cells. Hence, it is an immunotherapy medication rather than a chemotherapeutic treatment.
Amyloidosis
Amyloidosis is an extremely rare protein disorder affecting the organs. It causes a build-up of amyloid. Various organs like the heart, kidney, liver, digestive system and nervous system could be affected in the process.
Dosage and Administration:
Daratumumab is a liquid solution that is available in a single vial. It may or may not be mixed with other solutions before injecting intravenously. The dose is available in the following forms:
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100 milligrams per 5 milliliters.
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400 milligrams per 20 milliliters.
The drug dosage is calculated by the individual's body weight. It is usually 16 mg per kg of body weight. The drug is mixed with 0.9 percent sodium chloride before infusing intravenously. The doctor will decide the best dosage depending on the body type and the severity of the condition. The drug is administered either intravenously or subcutaneously with the help of an injection. Care should be taken while administering the drug to avoid any kind of cross-contamination.
Drug Interactions
Daratumumab has the potential to interact with various drugs; however, it possesses limited adverse effects. Hence, a proper drug history can help to limit drug interactions and associated complications with the drug.
Warnings
Before using any medication, it is important to understand the risk weighed against the benefits of the drug. The following should be considered before taking the medication.
Allergies
Informing the doctor regarding any unusual allergic reactions to the medicine or any other medication is extremely important. Also, informing any other type of allergies like food or duster allergies can be helpful.
Pediatric
The safety and efficacy of the medication are yet to be determined in the pediatric population. Also, age-related effects are yet to be established; hence, it is better to avoid them in newborns and young children.
Geriatric
The usefulness of the drug in the elderly population may have a lot of complications due to their pre-existing conditions. It may cause serious and unwanted effects like pneumonia and sepsis. Hence, it is safer to avoid the drug unless necessary.
Breastfeeding
The drug is yet to be proven safe in pregnant and feeding mothers. Hence, outweighing the risk is important for such individuals to understand the clear consequences.
Kidney Disorders
Individuals with pre-existing kidney disorders should inform the doctor about their health condition. The drug gets metabolized in the kidneys, so overworking the kidneys could cause kidney failure.
Precautions
While infusing the medication, an allergic reaction or anaphylaxis could occur, which is life-threatening. It is important to inform the doctor in case of experiencing symptoms like chest tightness or blurred vision. In some cases, the platelet count may gradually decrease in the initial phase of treatment. Individuals who have previously encountered hepatitis have to be extremely careful during drug intake, as it tends to reactivate the virus.
Monitoring and Testing
Before starting the drug, a blood test may be done to check for any pre-existing health conditions. The drug can temporarily lower the white blood count and the platelet count, which may gradually elevate with time. However, the lack of increase in the white blood cell should be strictly monitored, and the dosage should be altered by the health care professional accordingly.
For Patients
What Is Multiple Myeloma?
Multiple myeloma is a bone marrow cancer that affects the plasma cells. The immune system has several types of cells that help to fight infections. The most important cells are the lymphocytes, which are a type of white blood cell. Generally, the plasma cells make antibodies that help to fight any infection. In multiple myeloma, since the plasma cells are affected, the immunity of the individual is drastically compromised.
What Is Daratumamab?
Daratumumab treats multiple myeloma in combination with a few drugs by boosting the immune system and playing an important role in maintaining the healthy cells of the body from being affected by the disease. It is a monoclonal antibody that fights the disease and helps to keep the harmony of the immune system.
How Is Daratumumab Used?
The FDA-approved drug can be used alone or in combination with other drugs. It is infused into the vein over eight hours. The infusion time may be shortened or extended, depending on the level of tolerance after the first infusion. Usually, a nurse or a trained healthcare professional will administer the drug. The needle is pricked through one of the veins, and the drug is slowly infused. The drug is given at regular intervals and is strictly monitored for any side effects.
The timeline of the drug could usually be up to 25 weeks. In the first eight weeks, the drug is given once every week. From the ninth week to the twenty-fourth week, the drug is administered once every two weeks. After the twenty-fifth week, the drug is administered once every four weeks. A shot of anti-viral medicine may be given within one week after starting the treatment to prevent the occurrence of any viral infections caused by shingles.
Missed Dose
The medicine has to be administered in regular doses; missing a dose is not appreciated. However, in such cases, contacting the healthcare professional can be useful to guide through the process and regularize the drug intake.
When Is Daratumumab Prescribed?
The drug is specifically given in the treatment of multiple myeloma. It is also additionally beneficial for certain types of cancers in which chemotherapy is not sufficient to kill the cancer cells. So, Daratumumab is used as an alternative method. The drug is used in combination with cancer medication and a few steroid drugs.
What Are the Factors Influencing Daratumumab Dosage?
Various factors influence Daratumumab dosage, which are mentioned below:
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The weight of an individual is the most important factor. Being overweight and underweight may influence the outcome of the treatment and the efficacy of the drug.
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The time duration after which the treatment started from the first diagnosis of multiple myeloma.
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Any other pre-existing medical conditions.
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The response of the body to the drug.
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Any drug interaction that may influence the scope of the drug.
What Are the Side Effects of Daratumamab?
The side effects of the drug may vary with each individual, depending on their medical history and current intake of medicine. Some of the most common side effects of the drug are mentioned below:
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Fatigue or tiredness.
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Back pain.
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Joint pain.
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Constipation or diarrhea.
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High blood pressure.
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Muscle pain.
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Puffiness of eyelids.
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Nervousness.
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Increase in heart rate.
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Sore throat.
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Stuffy nose.
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Vomiting.
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Ear congestion.
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Dizziness.
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Loss of appetite.
The most uncommon side effect of the drug is infusion reaction. This generally occurs after an individual is infused with the drug for the first time. The symptomatic manifestations include:
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Shortness of breath.
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Cough.
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Wheezing.
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Hives.
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Itching.
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Rash.
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Chills.
Usually, the symptoms tend to resolve on their own in most cases. However, the patients must be monitored closely for appropriate drug administration and to prevent allergic reactions. Also, most side effects do not occur in every population. But it is better to inform the medical health professional in case of such unusual experiences.
What Are the Special Precautions to Be Followed When Using Daratumumab?
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Before starting the treatment, give the healthcare professional a proper history of medications.
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Avoid drugs like Aspirin unless instructed by the doctor.
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It is safe to avoid any kind of vaccination or immunization without the approval of the doctor.
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In the case of pregnant women or those planning any pregnancy, the drug can be unsafe for the fetus (child), as it may cause birth defects.
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It is safer for both men and women to use contraceptives (birth control) during the course of treatment and for at least three months post-treatment.
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Do not breastfeed the child while taking this medication.
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It is important to avoid alcoholic beverages.
What Are the Self-Care Tips to Be Followed During the Intake of Daratumumab?
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Drink plenty of water during the drug intake to eliminate toxins from the body.
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It is better to avoid crowded areas as the affected individual may be highly prone to infections.
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It is important to wash hands regularly, to avoid any infections from entering the body and causing any serious health implications.
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Also, it would be safe to avoid contact sports.
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Eating small meals can help reduce nausea and vomiting during the drug intake.
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It is vital to take enough rest so that the body can heal well.
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It is important to stay active during the drug intake. So regular walks are encouraged. However, it is better to avoid strenuous exercise to prevent complications.
For Doctors
Mechanism of Action
Many previous studies have interpreted that MM cell death is induced via Daratumumab, especially the complement-dependent cytotoxicity and the antibody-dependent cell-mediated toxicity. Other mechanisms include antibody-dependent cellular phagocytosis and apoptosis.
Pharmacodynamics
Daratumumab is an anti-cancer drug that works by targeting cancer cells. Hence, it is called targeted therapy. The drug targets CD38, a cell surface glycoprotein. CD38 is highly expressed in myeloma cells. The drug inhibits the growth of tumor cells on binding to CD38 by mediating cell lysis through cytotoxicity and antibody-dependent cellular phagocytosis.
Involvement of the Healthcare Team
Healthcare professionals play a crucial role in monitoring the condition and administering doses appropriately in affected individuals. The doses may be altered depending on the speed of recovery of the individual. Good teamwork can definitely help with better outcomes in the condition. It is important to have regular follow-ups to evaluate the overall health condition of the individual and cater to the treatment so that the individual enjoys maximum benefit and healthy life.
What Are the Studies on Daratumumab?
Various clinical trials are conducted to understand the safety and efficacy of Daratumumab in patients with multiple myeloma. The study was conducted on participants with a minimum of three prior lines of therapy. Approximately 150 participants were screened and treated. Post-treatment, the patients were followed-up to understand the prognosis. The participants receive an intravenous infusion of the drug for almost a month until there is disease progression or unacceptable toxicity. Pre and post-infusion medications were given to prevent any allergic reaction. The overall response of the individuals to the drug proved the efficacy of the medication. The study is still being continued, and the follow-up is till the lifetime of the participants.
