Daratumumab

Daratumumab (Darzalex) is used to treat multiple myeloma to help slow or stop cancer from progressing. Daratumumab is a targeted cancer medicine that binds to a protein on the surface of myeloma cells, it then kills the cancer cells, and also helps the immune system to fight cancer better. It can be used alone as a single therapy but is often used together with other medicines, depending on your clinical situation.

Daratumumab is an infusion that is given into a vein over a period of hours by your healthcare provider. Daratumumab subcutaneous injection is a different product as it contains both daratumumab and hyaluronidase-fihj (Brand name Darzalex Faspro) which is given as an injection under the skin over 3 to 5 minutes.

FDA approval for Daratumumab (Brand name Darzalex) was granted on November 16, 2015, for multiple myeloma patients who had previously had other treatments. Darzalex approval has been extended to treat a range of patients with different treatment regimes. Darzalex Faspro FDA approval was received on May 1, 2023, it is the subcutaneous form of Darzalex.

Daratumumab mechanism of action (MOA) is by binding to the CD38 protein on the surface of the multiple myeloma cells which it then kills, daratumumab also helps to increase the ability of the immune system to fight cancer. Daratumumab is a monoclonal antibody that is designed to fit together like a lock and key to the antigen CD38 on myeloma cells. It is called a targeted therapy because it specifically targets the CD38 which are overexpressed on the multiple myeloma cells. Daratumumab is from a class of medicines called CD38 monoclonal antibodies.

Daratumumab is not a chemotherapy, it is a targeted cancer medicine.

The difference between Darzalex and Darzalex Faspro is the number of active ingredients, how they are given, the specific conditions they treat, and the number of systemic administration-related reactions.

• Daratumumab (Darzalex) contains one active ingredient, and is given intravenously over several hours and is used to treat specific multiple myeloma patients.
• Darzalex Faspro contains both daratumumab and hyaluronidase-fihj, and is given subcutaneously over 3 to 5 minutes. Darzalex Faspro is used to treat specific multiple myeloma patients and is also FDA-approved to treat adults with newly diagnosed light chain (AL) amyloidosis.
• Darzalex Faspro advantages over Darzalex are that it is faster to administer, it has less systemic administration-related reactions (ARRs), and is also indicated to treat adults with newly diagnosed light chain (AL) amyloidosis as well as adults with certain multiple myeloma.

Click this link for more information on Darzalex Faspro.

Daratumumab is given as an infusion into a vein over a period of hours by your healthcare provider.

Daratumumab is usually given every 1 to 3 weeks during the first several weeks of treatment. Then it is given once every 4 weeks until your body no longer responds to the medicine. Your doctor will determine how long to treat you with this medicine.

You may be given other medications before and after your infusion to help prevent serious side effects or an allergic reaction (infusion-related reactions). Keep using these medicines for as long as your doctor has prescribed.

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

If you need to receive a blood transfusion, be sure to tell your caregivers that you are being treated with daratumumab as it can affect blood tests that are used to match your blood type. This medicine can affect blood-typing tests for up to 6 months after you stop using this medicine.

If you've ever had hepatitis B, using daratumumab can cause this virus to become active or get worse. Tell your doctor if you don't feel well and you have right-sided upper stomach pain, vomiting, loss of appetite, or yellowing of your skin or eyes. You may need frequent liver function tests while using this medicine and for several months after you stop.

Daratumumab 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.

Men and women should carefully follow all instructions about the use of birth control while you are using daratumumab in combination with other medicines. See Pregnancy information below.

You should not be treated with this medicine if you are allergic toit or any of the inactive ingredients.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• a breathing disorder; or
• herpes zoster (also called shingles) you may be prescribed antiviral medicine to prevent reactivation of shingles.
• hepatitis B as hepatitis B virus may become active again. Tell your healthcare provider right away if you get worsening tiredness or yellowing of your skin or the white part of your eyes.
• have hereditary fructose intolerance (HFI). This medicine contains sorbitol which is a source of fructose. People with HFI cannot break down fructose, which may cause serious side effects.

Pregnancy

Daratumumab

• Daratumumab may harm an unborn baby.

• Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with this medicine.
• Females who are able to become pregnant should use an effective method of birth control during treatment and for 3 months after their last dose of Darzalex. Talk to your healthcare provider about birth control methods that you can use during this time.

Daratumumab in combination with lenalidomide, pomalidomide, or thalidomide.

• Both men and women using these other drugs must use effective birth control.
• Even one dose can cause severe, life-threatening birth defects or death of a baby, if the mother or the father is taking lenalidomide, pomalidomide, or thalidomide at the time of conception or during pregnancy.
• Before starting Darzalex in combination with lenalidomide, pomalidomide, or thalidomide, females and males must agree to the instructions in the lenalidomide, pomalidomide, or thalidomide REMS program.

Breastfeeding

If you are breastfeeding or plan to breastfeed. It is not known if this medicine passes into your breast milk. You should not breastfeed during treatment with this medicine. Talk to your healthcare provider about the best way to feed your baby during treatment with Darzalex.

Common daratumumab side effects

Common daratumumab side effects may include nausea, constipation, diarrhea, fever, shortness of breath, nerve problems causing tingling, numbness, or pain, feeling tired or weak, swelling in your hands, ankles, or feet and also cold symptoms such as stuffy nose, sneezing, cough, sore throat.

Serious daratumumab side effects

Get emergency medical help if you have signs of an allergic reaction: hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, itchy, or nauseated or if you have a headache, stuffy nose, runny nose, cough, fever, chills, wheezing, trouble breathing, or a tight feeling in your throat.

Daratumumab may cause other serious side effects. Call your doctor at once if you have:

• cough with yellow or green mucus;
• stabbing chest pain, wheezing, feeling short of breath;
• numbness, tingling, burning pain; or
• low blood cell counts - fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Daratumumab is FDA-approved to treat:

• newly diagnosed patients who cannot have autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy. Daratumumab is to be used in combination with lenalidomide and dexamethasone
• newly diagnosed patients who cannot have autologous stem cell transplant combination. Daratumumab is to be used in combination with bortezomib, melphalan, and prednisone.
• newly diagnosed patients who can have an autologous stem cell transplant, when used in combination with bortezomib, thalidomide, and dexamethasone.
• patients who have received at least one prior multiple myeloma medical treatment. Daratumumab is to be used in combination with bortezomib and dexamethasone.
• patients with relapsed or refractory multiple myeloma who have received one to three prior multiple myeloma medical treatments. Daratumumab is to be used in combination with carfilzomib and dexamethasone.
• patients who have received at least two prior medical treatments, including lenalidomide and a proteasome inhibitor. Daratumumab to be used in combination with pomalidomide and dexamethasone.
• patients who have received at least three prior medical treatments, including a proteasome inhibitor (PI) and an immunomodulatory agent that they have not responded to. Daratumumab can be used alone as a single therapy.

Usual Adult Dose Daratumumab 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; 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; 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; 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 prior to initiating therapy.

Daratumumab J code is J9145 (Injection, daratumumab, 10 mg - Darzalex brand)

Daratumumab and hyaluronidase J code is J9144 (Injection, daratumumab, 10 mg and hyaluronidase-fihj - Darzalex Faspro brand))

J codes are important, accurate, and consistent coding for billing and reimbursement purposes. J codes are used for medicines that are not taken orally and include injections, inhalations chemotherapies. Your physician will need the infusions J-code when filling out forms for your treatment.

Call your doctor for instructions if you miss an appointment for your Darzalex injection.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Other drugs may interact with daratumumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Review the full Daratumumab Package Insert (Darzalex brand) for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about Darzalex for safe and effective use and does not take the place of talking to your doctor about your treatment.

Daratumumab Package Insert is sometimes called Daratumumab HCP or Daratumumab Prescribing Information.

• Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Do not freeze or shake.
• Protect from light.
• This product contains no preservatives.

Active ingredient: daratumumab

Darzalex brand 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.

Daratumumab manufacturer is Janssen Biotech, Inc., Horsham, PA 19044, USA - for the Darzalex Brand.