Darzalex

Darzalex (daratumumab) is a targeted monoclonal antibody used to treat multiple myeloma, a cancer that affects plasma cells in the bone marrow, in adults. Darzalex is given as an intravenous (IV) infusion over several hours, and Darzalex Faspro is given as an injection under the skin (subcutaneous injection) over 3 to 5 minutes.

Darzalex works by binding to a protein called CD38, which is found at high levels on the surface of multiple myeloma cells, and by triggering the body's immune system to destroy them. Darzalex is a CD38-directed cytolytic antibody.

Darzalex is not chemotherapy; it is a targeted therapy.

Darzalex is often used alongside other medicines such as bortezomib, lenalidomide, or dexamethasone.

Darzalex received its first FDA approval on November 16, 2015, for the treatment of multiple myeloma in previously treated patients. Since then, the FDA has expanded its approval to cover a broader range of patients across multiple treatment regimens.

Darzalex is FDA-approved to treat multiple myeloma in certain adults. It is approved for use for:

• Newly diagnosed - transplant eligible: for patients recently diagnosed who are candidates for an autologous stem cell transplant
• Newly diagnosed - transplant ineligible: for patients recently diagnosed who are not candidates for a stem cell transplant
• Relapsed or refractory multiple myeloma: for patients whose myeloma has come back after specific treatment (relapsed) or has stopped responding to treatment (refractory)
• Previously treated multiple myeloma: for patients who have received at least one prior therapy.

Darzalex FDA-approved indications

Darzalex is FDA-approved to treat multiple myeloma in specific adult patients, on its own or in combination with other medicines. Your oncologist will determine which combination is right for you based on your treatment history and overall health.

Newly diagnosed multiple myeloma

• Eligible for autologous stem cell transplant Darzalex (D) + bortezomib (V) + thalidomide (T) + dexamethasone (d) = DVTd.
• Ineligible for autologous stem cell transplant Darzalex + bortezomib + melphalan (M) + prednisone (p) = DVMp. Darzalex + lenalidomide (R) + dexamethasone (d) = DRd.

Relapsed or refractory multiple myeloma

• After ≥1 prior therapy Darzalex + lenalidomide + dexamethasone = DRd.
• After 1- 3 prior lines of therapy Darzalex + carfilzomib (K) + dexamethasone = DKd.

Previously treated multiple myeloma

• After at least 1 prior line of therapy Darzalex + bortezomib + dexamethasone = DVd.
• After at least 2 prior lines of therapy Darzalex + pomalidomide (P) + dexamethasone (d) = DPd in patients who have received at least 2 lines of therapy, including lenalidomide and a proteasome inhibitor (PI).
• After ≥3 prior therapies Darzalex monotherapy, in patients who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.

Darzalex is given as a slow intravenous (IV) infusion by a healthcare provider at a clinic or hospital. The first infusion takes approximately 7 to 8 hours to reduce the risk of reactions. The second infusion can be given over about 4 hours, and subsequent infusions over approximately 3 hours as the risk of reactions decreases. Darzalex Faspro (daratumumab and hyaluronidase) is a faster alternative given as a subcutaneous injection over 3–5 minutes.

How often is Darzalex given?

Darzalex is given weekly or every 2–3 weeks at the start of treatment, then reduced to once every 4 weeks as maintenance, depending on your treatment regimen.

How long is Darzalex treatment?

Treatment continues until your myeloma stops responding to Darzalex or side effects become unacceptable. Your doctor will determine the right duration for you.

Before and after your infusion

• Pre-infusion medications: A corticosteroid, antipyretic (such as acetaminophen), and antihistamine are given 1 to 3 hours before every infusion to reduce the risk of reactions
• Post-infusion medications: A corticosteroid is required after each infusion; monotherapy patients take this orally for 2 days after each infusion
• COPD patients: Additional bronchodilators and inhaled corticosteroids may be prescribed, and can be discontinued after the first 4 infusions if no major reaction occurs
• Infusion reactions: Your care team will stop the infusion immediately if a reaction occurs. Darzalex is permanently discontinued for life-threatening reactions
• Missed dose: Administer as soon as possible and adjust the schedule to maintain the correct interval

Low blood cell counts - neutropenia and thrombocytopenia

Darzalex can reduce white blood cell counts (neutropenia) and platelet counts (thrombocytopenia). Your doctor will monitor your blood counts regularly and may delay treatment if levels drop. Tell your doctor right away if you develop fever, chills, unusual bruising, or bleeding.

Infections

Darzalex can cause serious life-threatening infections that can lead to death. Tell your healthcare provider right away if you develop a fever, trouble breathing, cough, burning or pain when you urinate, or any other signs and symptoms of infection during treatment.

Blood transfusions - interference with blood typing tests

Darzalex can interfere with the indirect antiglobulin (Coombs) test used for blood typing. This effect can last up to 6 months after your last dose. Always tell your care team and any blood bank that you are receiving Darzalex before any transfusion or blood typing test.

Hepatitis B reactivation

If you have ever had hepatitis B, Darzalex may reactivate the virus. Your doctor will test for hepatitis B before starting treatment and monitor liver function during and for several months after treatment. Tell your doctor right away if you develop yellowing of the skin or eyes, right-sided stomach pain, or unusual tiredness.

Interference with myeloma monitoring tests

Darzalex can show up on blood protein tests (serum protein electrophoresis and immunofixation assays) used to track your myeloma, causing false positive results. Your doctor is aware of this and can use a specific test to tell the difference between Darzalex and myeloma protein in your blood.

Shingles (herpes zoster) reactivation

If you have had shingles before, Darzalex may trigger a reactivation. Antiviral medicine should be started within 1 week of beginning treatment and continued for 3 months after your last dose.

Hereditary fructose intolerance

Darzalex contains sorbitol, a source of fructose. Tell your doctor before starting treatment if you have hereditary fructose intolerance (HFI).

Darzalex is contraindicated in patients with a history of severe hypersensitivity (e.g., anaphylactic reactions) to daratumumab or any of the components of the formulation. Do not use Darzalex if you have had a prior anaphylactic reaction to this medicine.

Tell Your Doctor If You Have:

• A history of severe hypersensitivity or anaphylaxis to daratumumab (contraindication — see above)
• A breathing disorder such as chronic obstructive pulmonary disease (COPD) — you may require additional post-infusion medications, including short- and long-acting bronchodilators and inhaled corticosteroids, to manage respiratory complications
• A history of hepatitis B
• Had shingles (herpes zoster) before
• Hereditary fructose intolerance (HFI)
• Any current medicines, vitamins, or herbal supplements, as drug interactions are possible

Your doctor will perform blood typing and screening (type and screen) before you start Darzalex.

Common Side Effects (occurring in 20% or more of patients)

The most frequently reported side effects from FDA clinical trials include:

• Upper respiratory infection (e.g., stuffy nose, sore throat, sneezing, cough)
• Neutropenia (low white blood cell count, which may increase risk of infection)
• Infusion-related reactions (see below)
• Thrombocytopenia (low platelet count may increase risk of bleeding)
• Anemia (low red blood cell count, which may cause fatigue or pale skin)
• Diarrhea or constipation
• Peripheral sensory neuropathy (tingling, numbness, or nerve pain)
• Fatigue or weakness (asthenia)
• Peripheral edema (swelling in hands, ankles, or feet)
• Nausea
• Cough
• Fever
• Dyspnea (shortness of breath)

Infusion-Related Reactions

Infusion-related reactions are common, particularly with the first infusion. Tell your care team right away if, during or after the infusion, you experience:

• Dizziness, itching, or headache
• Stuffy or runny nose, sneezing, or cough
• Fever or chills
• Wheezing, difficulty breathing, or a tight feeling in the throat
• Nausea

Your care team will stop the infusion if a reaction occurs and will manage it appropriately. Darzalex must be permanently discontinued in cases of anaphylaxis or life-threatening reactions.

Serious Side Effects – Seek Emergency Help Immediately If You Experience:

• Severe allergic reaction (anaphylaxis): hives, difficulty breathing, swelling of the face, lips, tongue, or throat
• Signs of serious infection: fever, chills, cough with yellow or green mucus
• Chest pain or severe shortness of breath
• Signs of low blood cell counts: unusual bleeding or bruising, pale skin, feeling light-headed, cold hands and feet
• Liver problems (especially with prior hepatitis B): yellowing of skin or eyes, upper right stomach pain, vomiting, loss of appetite

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects.

Your treatment may be paused or permanently stopped if serious side effects occur. Report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. You may also contact Janssen Biotech at 1-800-JANSSEN.

Usual Adult Darzalex Dose for Multiple Myeloma

Dosing schedule in combination with lenalidomide or pomalidomide (4-week cycle) and low-dose dexamethasone, and for monotherapy:

• Weeks 1 to 8: 16 mg/kg IV weekly (total of 8 doses).
• Weeks 9 to 24: 16 mg/kg IV every 2 weeks (total of 8 doses); first dose of the every-2-week dosing schedule is given at Week 9.
• Week 25 and onwards until disease progression: 16 mg/kg IV every 4 weeks; the first dose of the every-4-week dosing schedule is given at Week 25.

Dosing schedule in combination with bortezomib, melphalan, and prednisone, 6-week cycle:

• Weeks 1 to 6: 16 mg/kg IV weekly (total of 6 doses).
• Weeks 7 to 54: 16 mg/kg IV every 3 weeks (total of 16 doses); first dose of the every-3-week dosing schedule is given at Week 7.
• Week 55 onwards until disease progression: 16 mg/kg IV every 4 weeks; the first dose of the every-4-week dosing schedule is given at Week 55.

Dosing schedule in combination with bortezomib, thalidomide, and dexamethasone 4-week cycle:

Induction

• Weeks 1 to 8: 16 mg/kg IV weekly (total of 8 doses).
• Weeks 9 to 16: 16 mg/kg IV every 2 weeks (total of 4 doses); first dose of every-2-week dosing schedule is given at Week 9.
• Stop for high-dose chemotherapy and ASCT.

Consolidation

• Weeks 1 to 8: 16 mg/kg IV every 2 weeks; first dose of the every-2-week dosing schedule is given at Week 1 upon reinitiation of therapy following ASCT.

Dosing schedule in combination with bortezomib and dexamethasone, 3-week cycle:

• Weeks 1 to 9: 16 mg/kg IV weekly (total of 9 doses).
• Weeks 10 to 24: 16 mg/kg IV every 3 weeks (total of 5 doses); first dose of every-3-week dosing schedule is given at Week 10.
• Week 25 onwards until disease progression: 16 mg/kg IV every 4 weeks; first dose of the every-4-week dosing schedule is given at Week 25.

Dosing schedule with carfilzomib and dexamethasone 4-week cycle:

• Week 1: 8 mg/kg IV on Days 1 and 2 (total of 2 doses)
• Weeks 2 to 8: 16 mg/kg IV weekly (total of 7 doses).
• Weeks 9 to 24: 16 mg/kg IV every 2 weeks (total of 8 doses); first dose of the every-2-week dosing schedule is given at Week 9.
• Week 25 onwards until disease progression: 16 mg/kg every 4 weeks; the first dose of the every-4-week dosing schedule is given at Week 25.

Comments:

• Dosing is based on actual body weight.
• The first 16 mg/kg dose at Week 1 may be split over 2 consecutive days (i.e., 8 mg/kg on Day 1 and Day 2, respectively.
• Pre-and post-infusion medications should be given before initiating therapy.

You will need frequent medical tests while having treatment with this medicine.

Pregnancy

Darzalex can cause fetal harm when administered to a pregnant woman. Tell your doctor immediately if you become pregnant or think you may be pregnant during treatment.

Birth Control

• Females: use effective contraception during treatment and for 3 months after the last dose
• If combined with lenalidomide, pomalidomide, or thalidomide: both males AND females must follow strict birth control requirements under the REMS program. Even one dose of these medicines can cause severe, life-threatening birth defects or fetal death

Before starting these combination therapies, you will need to agree to the requirements of the lenalidomide, pomalidomide, or thalidomide REMS program, which includes birth control, pregnancy testing, and blood/sperm donation restrictions.

Breastfeeding

Do not breastfeed during Darzalex treatment. It is not known whether daratumumab passes into breast milk. Talk to your doctor about the safest way to feed your baby during treatment.

Darzalex may interact with other medicines, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements. There are no well-established major drug-drug interactions specific to daratumumab itself, but the medicines used alongside Darzalex — such as lenalidomide, bortezomib, thalidomide, and dexamethasone — each have their own interaction profiles. Tell your doctor about all medicines you are currently taking before starting Darzalex. Use the Darzalex drug interaction checker for a full personalized report.

Darzalex Faspro is a subcutaneous (under-the-skin) form of daratumumab. Here is how the two compare:

Darzalex Faspro (daratumumab and hyaluronidase) offers a significantly faster administration time and may suit patients who prefer a shorter visit.

Active ingredient: Daratumumab

Inactive ingredients: May include glacial acetic acid, L-histidine, L-histidine hydrochloride monohydrate, L-methionine, mannitol, polysorbate 20, sodium acetate trihydrate, sodium chloride, sorbitol, and water for injection (formulation varies by vial type).