Darzalex

Multiple Myeloma Treatment

Darzalex is primarily used to treat adults with multiple myeloma. It is approved for use in several different stages of the disease, depending on the patient's treatment history and eligibility for other procedures.

Newly Diagnosed Multiple Myeloma

For patients who have not yet received treatment for their condition, Darzalex may be prescribed in the following situations:

• Transplant-eligible patients: It is used in combination with other medications for those who are candidates for an autologous stem cell transplant.
• Transplant-ineligible patients: It is used in combination with other therapies for those who cannot undergo a stem cell transplant.

Relapsed or Refractory Multiple Myeloma

Darzalex is also used for patients who have already tried other treatments. This includes:

• Combination therapy: It may be used with other drugs for patients who have received at least one prior therapy.
• Monotherapy: It may be used alone for patients who have received at least three prior lines of therapy, including specific classes of drugs like proteasome inhibitors and immunomodulatory agents, or for those whose cancer did not respond to those treatments.

The medication works by targeting a specific protein called CD38 found on the surface of myeloma cells, which helps the immune system identify and attack the cancer.

Targeting Cancer Cells

Darzalex works by identifying and attaching to a protein called CD38. This protein is found in high amounts on the surface of multiple myeloma cells and some other types of blood cancer cells. Because CD38 is much more common on cancer cells than on healthy cells, the medication can specifically target the disease.

Immune System Activation

Once Darzalex binds to the CD38 protein, it acts like a signal for the body's immune system. It works through several different methods to eliminate the cancer:

• Immune-mediated cell death: The medication helps immune cells, such as natural killer cells and macrophages, recognize and kill the cancer cells.
• Direct cell death: Binding to the protein may trigger a process that causes the cancer cell to self-destruct.
• Complement-dependent cytotoxicity: The medication can activate a group of proteins in the blood called the complement system, which works to puncture and destroy the cancer cell membrane.

By reducing the number of myeloma cells in the body, Darzalex helps slow the progression of the disease and may improve symptoms.

Common Side Effects

Many people using Darzalex experience mild to moderate side effects. These may include:

• Fatigue or feeling weak
• Nausea, diarrhea, or constipation
• Fever and chills
• Cough and shortness of breath
• Upper respiratory tract infections, such as the common cold
• Back pain or joint pain
• Swelling in the hands, ankles, or feet
• Dizziness or headache
• Trouble sleeping

Serious Side Effects

Some side effects require immediate medical attention. Contact a healthcare provider right away if you experience:

• Infusion-related reactions: These are most common during the first dose and can include itchy skin, rash, hives, throat tightness, wheezing, or dizziness.
• Low blood cell counts: Darzalex can lower white blood cell counts (increasing infection risk), red blood cell counts (causing anemia), and platelets (increasing bruising or bleeding risk).
• Infections: Serious infections like pneumonia or the reactivation of viruses such as shingles (herpes zoster) or hepatitis B.

Healthcare providers often prescribe medications before and after treatment to help prevent or manage these side effects.

Infusion-Related Reactions

Infusion-related reactions are common and can be severe or life-threatening. These reactions often occur during the first infusion but can happen at any time. Symptoms may include respiratory issues like wheezing or shortness of breath, as well as dizziness, nausea, and skin rashes. Pre-infusion and post-infusion medications, such as corticosteroids and antihistamines, are typically prescribed to manage these risks.

Interference with Blood Compatibility Testing

Daratumumab binds to CD38 on red blood cells, which interferes with the indirect antiglobulin test (Coombs test) used for blood typing and cross-matching. This interference can persist for up to six months after treatment ends. Healthcare providers must perform blood typing and screening before the first dose is administered to ensure safe blood transfusions if they become necessary.

Neutropenia and Thrombocytopenia

Treatment may lead to significant decreases in white blood cell counts (neutropenia) and platelet counts (thrombocytopenia). These conditions increase the risk of infection and bleeding. Monitoring of complete blood counts is required throughout the treatment period to manage these risks.

Hepatitis B Virus Reactivation

Reactivation of the Hepatitis B virus (HBV) has been reported in patients treated with CD38 antibodies, including fatal cases. Patients are screened for HBV before starting therapy. If reactivation occurs, treatment may need to be interrupted or discontinued while the infection is managed.

Interference with Laboratory Tests

This medication can interfere with certain laboratory tests used to monitor disease response, such as serum protein electrophoresis and immunofixation assays. This interference may affect the assessment of treatment effectiveness in patients with certain types of myeloma.

Embryo-Fetal Toxicity

Based on its mechanism of action, Darzalex may cause harm to an unborn baby. Females who can become pregnant should use effective contraception during treatment and for at least three months after the final dose.

Pregnancy

There is limited information regarding the use of Darzalex in pregnant women. Because Darzalex is a monoclonal antibody, it can cross the placenta and may affect the developing fetus. Based on its mechanism of action, it could cause fetal harm, including a decrease in certain immune cells in the newborn.

Healthcare providers typically recommend the following for individuals who can become pregnant:

• A pregnancy test should be performed before starting treatment.
• Effective contraception should be used during treatment and for at least 3 months after the final dose.

If Darzalex is used in combination with other medications, such as lenalidomide, thalidomide, or pomalidomide, additional strict pregnancy prevention requirements must be followed. Those drugs are known to cause severe birth defects and have specific safety programs in place.

Breastfeeding

It is not known whether Darzalex passes into human breast milk or how it might affect a nursing infant. Because many antibodies are excreted in human milk and there is a potential for serious adverse reactions in the infant, breastfeeding is generally not recommended during treatment with Darzalex. Patients should discuss the best way to feed their baby with their healthcare provider.

Dosage Forms

Darzalex is provided as a sterile, preservative-free solution for intravenous use. The liquid is clear to opalescent and may range from colorless to pale yellow.

• Intravenous Infusion: This medication is supplied in single-dose vials. It must be diluted with a compatible solution by a healthcare professional before being administered into a vein.

Darzalex is not available in oral forms, such as tablets or capsules, and is only administered in a clinical setting by trained medical staff.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved Darzalex in November 2015. It was the first monoclonal antibody approved to treat multiple myeloma. Since its initial approval, the FDA has expanded its indications to include use in combination with various other therapies for patients at different stages of the disease, including those who are newly diagnosed.

Approved Indications

Darzalex is approved for the treatment of adult patients with:

• Newly diagnosed multiple myeloma, used in combination with other medications for patients who are or are not eligible for a stem cell transplant.
• Relapsed or refractory multiple myeloma, used as a single agent or in combination with other standard cancer treatments.
• Light chain (AL) amyloidosis, specifically the subcutaneous formulation, in combination with other therapies.

Safety Monitoring and Communications

The FDA monitors the safety of Darzalex through post-marketing surveillance. In 2020, the FDA identified potential signals of serious risks, including the risk of hepatitis B virus reactivation in patients receiving daratumumab. Regulatory guidelines recommend that healthcare providers screen patients for hepatitis B infection before starting treatment and monitor for signs of reactivation during therapy.

Darzalex does not currently have a boxed warning or a Risk Evaluation and Mitigation Strategy (REMS) program required by the FDA.

Factors Influencing Cost

Several factors determine the total cost of treatment with Darzalex:

• Dosage and Frequency: The amount of medication needed is often based on the patient's body weight. Additionally, the frequency of doses changes throughout the treatment course, typically starting weekly and moving to every few weeks.
• Administration Fees: Because Darzalex is administered by a healthcare professional as an intravenous infusion or a subcutaneous injection, there are costs associated with the clinical visit and the administration process itself.
• Treatment Setting: Costs may differ depending on whether the medication is received at a hospital outpatient department, a private clinic, or a specialized infusion center.

Insurance and Financial Support

Most insurance plans, including Medicare and private health insurance, provide coverage for Darzalex when it is medically necessary. However, patients may still be responsible for out-of-pocket expenses such as deductibles, co-insurance, or copayments.

Financial assistance programs may be available through the drug manufacturer or third-party organizations to help eligible patients manage these costs. These programs often include savings cards for those with commercial insurance or patient assistance programs for those who are uninsured or underinsured.

Generic and Biosimilar Availability

Darzalex is a brand-name biologic medication. Currently, there are no lower-cost biosimilar or generic versions available on the market. Biologic drugs are complex to manufacture, which generally contributes to their higher cost compared to traditional chemical drugs.