Daratumumab

Multiple Myeloma

Daratumumab is primarily used to treat multiple myeloma, a type of cancer that affects plasma cells in the bone marrow. It is prescribed in several different clinical situations:

• Newly Diagnosed: It is used for patients who are eligible for a stem cell transplant and for those who are not candidates for the procedure. In these cases, it is typically used in combination with other chemotherapy or immunotherapy drugs.
• Relapsed or Refractory: It is used for patients whose cancer has returned or did not respond to previous treatments. It may be used as a single agent or in combination with other medications for patients who have already received one or more prior lines of therapy.

Light Chain (AL) Amyloidosis

A specific formulation of this medication (daratumumab and hyaluronidase-fihj) is approved for use in adults with newly diagnosed light chain (AL) amyloidosis. This is a rare condition where abnormal proteins build up in organs such as the heart, kidneys, or liver. For this condition, it is used in combination with other medications.

Combination Therapy

Daratumumab is frequently prescribed as part of a multi-drug regimen. It is often used alongside corticosteroids and other specialized cancer medications, including:

• Bortezomib
• Lenalidomide
• Dexamethasone
• Thalidomide
• Pomalidomide
• Carfilzomib

Mechanism of Action

Daratumumab belongs to a class of medications known as monoclonal antibodies. These are laboratory-made proteins designed to target specific markers on cells in the body.

This medication works by attaching to a protein called CD38. This protein is found in high amounts on the surface of multiple myeloma cells and certain other abnormal cells, such as those involved in light chain (AL) amyloidosis.

Once daratumumab binds to the CD38 protein, it helps fight the disease through several mechanisms:

• Immune System Activation: It acts as a signal that helps the body's own immune system recognize, target, and kill the cancer cells.
• Direct Cell Death: The binding process can trigger the cancer cells to self-destruct or break down directly.
• Growth Inhibition: It may interfere with the signals that cancer cells need to grow and survive.

By focusing on cells that express CD38, the treatment aims to reduce the number of abnormal cells while minimizing the impact on many types of healthy cells.

Common Side Effects

Many people receiving daratumumab experience mild to moderate side effects. These may include:

• Fatigue or weakness
• Nausea, vomiting, diarrhea, or constipation
• Fever and chills
• Cough and shortness of breath
• Upper respiratory tract infections, such as the common cold
• Back pain, joint pain, or muscle spasms
• Swelling in the hands, ankles, or feet
• Headache or dizziness
• Trouble falling asleep or staying asleep

Infusion and Injection Reactions

Reactions can occur during or shortly after receiving daratumumab. These are common, especially during the first dose. Symptoms may include:

• Itching or rash
• Runny or stuffy nose
• Chest tightness or wheezing
• Difficulty breathing
• High blood pressure

Serious Side Effects

Some side effects can be severe and require medical attention. These include:

• Low blood cell counts: A decrease in white blood cells (which fight infection), red blood cells (which carry oxygen), or platelets (which help blood clot).
• Pneumonia: A serious lung infection.
• Hepatitis B reactivation: If you have previously had hepatitis B, the virus may become active again during treatment.

Infusion-Related Reactions

Serious and potentially life-threatening infusion-related reactions can occur. Symptoms may include coughing, wheezing, difficulty breathing, throat irritation, nausea, vomiting, chills, or changes in blood pressure. Healthcare providers typically administer medications such as corticosteroids, fever reducers, and antihistamines before and after the infusion to reduce this risk.

Interference with Blood Typing

Daratumumab binds to proteins on red blood cells, which can interfere with blood compatibility tests, specifically indirect antiglobulin tests (Coombs tests). This interference may persist for up to six months after the last dose. It is important for blood banks to be informed that a patient is receiving this medication before any blood transfusion is performed. Blood typing and screening are typically completed before starting treatment.

Decreased Blood Cell Counts

This medication can cause a significant decrease in white blood cell counts (neutropenia) and platelet counts (thrombocytopenia). These conditions can increase the risk of infections or bleeding. Regular complete blood cell counts are monitored during treatment to manage these risks.

Hepatitis B Reactivation

There is a risk of hepatitis B virus (HBV) reactivation in patients who have had the virus in the past. Screening for HBV is usually performed before starting treatment, and patients may be monitored for signs of reactivation during and after therapy.

Embryo-Fetal Toxicity

Based on its mechanism of action, daratumumab may cause harm to a developing fetus. Females of reproductive potential are advised to use effective contraception during treatment and for a specific period after the final dose.

Interference with Response Assessment

Daratumumab is a monoclonal antibody that can be detected on tests used to monitor the disease, such as serum protein electrophoresis (SPEP) and immunofixation assays. This may affect the ability to accurately assess the treatment response in some patients.

Pregnancy

Daratumumab may cause harm to an unborn baby. This medication is a monoclonal antibody that can cross the placenta and potentially affect the immune system of the fetus. It is important to notify a healthcare provider if you are pregnant or planning to become pregnant before starting this treatment.

Contraception

Individuals of reproductive potential are advised to use effective birth control during treatment and for at least 3 months after the last dose of daratumumab. Consult with a healthcare professional to determine the most appropriate method of contraception.

Breastfeeding

It is not known if daratumumab is present in human breast milk or if it could affect a nursing infant. Due to the potential for serious side effects, breastfeeding is typically not recommended during treatment and for 3 months following the final dose. Patients should discuss feeding options with their healthcare team.

Available Forms

Daratumumab is available in two primary formulations for administration by a healthcare professional:

• Solution for Intravenous Infusion: This formulation is provided in single-dose vials and must be diluted before being administered into a vein.
• Solution for Subcutaneous Injection: This formulation, which includes hyaluronidase-fihj, is provided in single-dose vials for injection under the skin.

FDA Approval and Indications

Daratumumab received its initial approval from the U.S. Food and Drug Administration (FDA) in 2015. It is primarily indicated for the treatment of adult patients with multiple myeloma, a cancer of the plasma cells. The medication is approved for use at various stages of the disease, including as a first-line treatment for newly diagnosed patients and as a therapy for those whose cancer has returned or failed to respond to previous treatments.

The FDA has also approved a subcutaneous formulation, which combines daratumumab with hyaluronidase-fihj, for the treatment of adults with light chain (AL) amyloidosis in combination with other specific chemotherapy regimens.

Recent Regulatory Updates

• In 2024, the FDA approved the subcutaneous formulation of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone for newly diagnosed patients with multiple myeloma who are eligible for an autologous stem cell transplant.
• The medication is also approved for the treatment of patients with high-risk smoldering multiple myeloma.

Safety and Monitoring Requirements

While daratumumab does not carry a Boxed Warning, the FDA requires specific safety protocols during its use. Healthcare providers must monitor patients for infusion-related or injection-related reactions, which are common and may require pre-treatment with corticosteroids or antihistamines.

Regulatory labeling also includes requirements for hepatitis B virus screening before starting the medication, as daratumumab can cause the virus to become active again in carriers. Additionally, because the drug can interfere with blood compatibility testing (cross-matching), patients are advised to carry an identification card informing healthcare providers of their treatment if they require a blood transfusion.

Factors Influencing Cost

Several factors determine the total cost of treatment with daratumumab, including:

• Dosage and Frequency: The amount of medication needed and how often it is administered (which typically changes throughout the course of treatment) impact the overall price.
• Administration Method: Daratumumab is available as an intravenous infusion or a subcutaneous injection. The costs for the medication and the professional services required to administer it may differ.
• Treatment Setting: Receiving the medication in a hospital outpatient department may result in different costs compared to a private clinic or specialized infusion center.

Insurance and Financial Assistance

Because daratumumab is a specialty biologic medication, most insurance providers, including Medicare and private plans, require prior authorization before approving coverage. Patients may still be responsible for out-of-pocket costs, such as deductibles, copayments, or coinsurance.

Financial assistance may be available for eligible patients through various channels:

• Manufacturer-sponsored patient assistance programs for those who are uninsured or underinsured.
• Copay savings cards for individuals with commercial insurance.
• Support from non-profit organizations and foundations that provide grants for specific medical conditions.

Patients should consult with their healthcare provider's billing office or their insurance company to obtain a precise estimate of their expected out-of-pocket expenses.