How it is administered

Isatuximab is given as an intravenous (IV) infusion, meaning it is delivered directly into your vein by a healthcare professional. The medication is available in single-dose vials containing either 100 mg/5 mL or 500 mg/25 mL (20 mg/mL concentration).

The infusion schedule varies depending on the combination regimen:

• With pomalidomide and dexamethasone or carfilzomib and dexamethasone: weekly infusions for the first cycle, then every two weeks.
• With bortezomib, lenalidomide, and dexamethasone: more frequent infusions during the first cycle, then every two weeks, and eventually every four weeks.

Premedication with acetaminophen, antihistamines, and corticosteroids is recommended to reduce the risk of infusion-related reactions.

How it works

Isatuximab is a monoclonal antibody that targets a protein called CD38, which is found on the surface of multiple myeloma cells and some other blood cells. By binding to CD38, isatuximab helps the immune system recognize and destroy cancer cells.

It works through several mechanisms:

• It directly induces cancer cell death (apoptosis).
• It activates immune cells, such as natural killer (NK) cells, to attack the cancer (antibody-dependent cell-mediated cytotoxicity, or ADCC).
• It helps other immune cells engulf and remove cancer cells (antibody-dependent cellular phagocytosis, or ADCP).
• It triggers the complement system, another part of the immune system, to kill cancer cells (complement-dependent cytotoxicity, or CDC).

Isatuximab can also suppress certain regulatory cells that may help cancer evade the immune system. When used in combination with other medications like pomalidomide, it can enhance the overall anti-tumor effect.

Who Should take it

Isatuximab is used for adults with multiple myeloma, a type of blood cancer that affects plasma cells. It is indicated in the following situations:

• In combination with pomalidomide and dexamethasone for patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
• In combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
• In combination with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients who are not eligible for autologous stem cell transplant.

It is important for patients to discuss with their healthcare provider whether isatuximab is appropriate for their specific situation, based on their prior treatments and overall health.

Who should not take it

Isatuximab should not be used in patients who have had a severe hypersensitivity (allergic) reaction to isatuximab or any of its ingredients.

It should also not be used during pregnancy, especially in combination with pomalidomide or lenalidomide, as these drugs can cause birth defects and are contraindicated in pregnant women. Women of childbearing potential should use effective contraception during treatment and for at least 5 months after the last dose.

There is limited information on its use in pediatric patients, and it is not approved for children. Patients with moderate or severe liver impairment should use caution, as the effects in this group are not well studied.

Commonly used with

Isatuximab is almost always used in combination with other medications for multiple myeloma. These include:

• Pomalidomide and dexamethasone
• Carfilzomib and dexamethasone
• Bortezomib, lenalidomide, and dexamethasone

These combinations are chosen based on your previous treatments and your doctor's recommendations.

Commonly tested with

Isatuximab has been tested in clinical trials with:

• Pomalidomide and dexamethasone (ICARIA-MM study)
• Carfilzomib and dexamethasone (IKEMA study)
• Bortezomib, lenalidomide, and dexamethasone (IMROZ study)

These combinations have shown improved outcomes for patients with multiple myeloma compared to regimens without isatuximab.