isatuximab

Isatuximab-irfc is a medication used in the treatment of adults with multiple myeloma who have received one or more prior lines of therapy. Multiple myeloma is a cancer of plasma cells, a type of white blood cells in the bone marrow. Isatuximab-irfc is a targeted drug that binds to a specific protein on the plasma cells, causing destruction of the cancer cells and enhancing immune activity against the cancer cells. Isatuximab-irfc is typically used in combination with an anticancer (antineoplastic) medication and dexamethasone, a corticosteroid.

Isatuximab-irfc is a humanized immunoglobulin G1 (IgG1) kappa monoclonal antibody produced in the lab. Isatuximab-irfc is designed to act against CD38, a protein that is found in some immune cells and is abundant on the surface of malignant plasma cells in multiple myeloma. CD38 protein is essential for the survival and proliferation of the malignant plasma cells. Blocking CD38 activity results in programmed death (apoptosis) of the cancer cells as well as activation of other immune mechanisms that kill the cancer cells.

Isatuximab-irfc is administered as an intravenous infusion with pre-medications including dexamethasone, acetaminophen, histamine H2 antagonists and diphenhydramine or equivalent to reduce the risk of infusion-related reactions. The FDA-approved uses of isatuximab-irfc are:

• Treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor, in combination with pomalidomide and dexamethasone
• Treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, in combination with carfilzomib and dexamethasone

• Do not use isatuximab-irfc in patients with severe hypersensitivity to isatuximab-irfc or any of its components.
• Isatuximab-irfc can cause serious infusion-related reactions including life-threatening and anaphylactic reactions.
  • Common symptoms include cough, nasal congestion, shortness of breath (dyspnea), and nausea. Serious symptoms include swelling, angioedema, bronchospasm, changes in blood pressure (hypertension or hypotension), and cardiac arrest.
  • Premedicate patients with dexamethasone, acetaminophen, histamine H2 antagonists and diphenhydramine or equivalent to reduce the risk and severity of infusion-related reactions.
  • Monitor patient’s vital signs and symptoms of reactions frequently during infusion. Based on the severity of reactions, interrupt, slow down or permanently discontinue isatuximab-irfc and institute appropriate treatment to manage infusion-related reactions.
• Isatuximab-irfc can deplete neutrophils and cause neutropenia and associated complications including febrile neutropenia and neutropenic infections.
  • Monitor patient’s blood cell counts periodically during treatment.
  • Monitor patients for signs of infection and consider use of antibiotic and antiviral prophylaxis during treatment.
• Isatuximab-irfc treatment is associated with increased incidence of second primary malignancies. Monitor patients for signs and symptoms of second primary malignancies.
• Isatuximab-irfc may interfere with certain blood tests. Use appropriate techniques for testing as recommended and exercise caution in interpretation of results.
• Isatuximab-irfc can cause depletion of fetal immune cells and bone density.
  • Advise women of pregnancy potential to use effective contraception for the recommended period.
  • Advise pregnant women of the potential risk to the fetus from isatuximab-irfc.
  • Do not use isatuximab-irfc and pomalidomide combination in pregnant women because pomalidomide can cause birth defects and death of the fetus. Refer to pomalidomide prescribing information for additional information.

Common side effects of isatuximab-irfc include:

• Blood disorders including:
  • Decrease in hemoglobin
  • Decrease in neutrophil immune cells (neutropenia)
  • Decrease in lymphocyte immune cells
  • Decrease in platelets
• Fever due to neutropenia (febrile neutropenia)
• Upper respiratory tract infection
• Pneumonia
• Bronchial inflammation (bronchitis)
• Infusion-related reactions including:
  • Cytokine release syndrome
  • Drug hypersensitivity
• Diarrhea
• Nausea
• Vomiting
• Shortness of breath (dyspnea)
• Cough
• Fatigue
• Weakness (asthenia)
• High blood pressure (hypertension)
• Infections
• Heart failure

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution

• 20 mg/mL (5-mL, 25-mL single-dose vial)

Adult:

Multiple myeloma

Combination with pomalidomide and dexamethasone

• Indicated, in combination with pomalidomide and dexamethasone, for multiple myeloma in adults who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor
• Each cycle is 28 days
• Refer to prescribing information of pomalidomide and dexamethasone for dosing information
• Cycle 1
  • 10 mg/kg (actual body weight) intravenous (IV) once every week (e.g., Day 1, 8, 15, 22)
• Cycle 2 and beyond
  • 10 mg/kg IV once every 2 weeks (e.g., Day 1, 15)
  • Continue until disease progression or unacceptable toxicity

Combination with carfilzomib and dexamethasone

• Indicated, in combination with carfilzomib and dexamethasone, for adults with relapsed or refractory multiple myeloma who have received 1-3 prior lines of therapy
• Each cycle is 28 days
• Refer to prescribing information of carfilzomib and dexamethasone for dosing information
• Cycle 1
  • 10 mg/kg (actual body weight) IV once every week (e.g., Day 1, 8, 15, 22)
• Cycle 2 and beyond
  • 10 mg/kg IV once every 2 weeks (e.g., Day 1, 15)
  • Continue until disease progression or unacceptable toxicity

Dosage Modifications

• No dose reduction recommended; dose delay may be required to allow recovery of blood counts if hematological toxicity occurs
• Refer to prescribing information for pomalidomide and dexamethasone for dosage modifications

Pediatric:

• Safety and efficacy not established

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Isatuximb-irfc has no listed severe, serious, moderate, or mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Based on its mechanism of action, isatuximab-irfc can cause fetal harm if used during pregnancy. No animal reproductive studies have been conducted and no data are available on the use of isatuximab-irfc in pregnant women to identify a drug-associated risk for major birth defects, miscarriages or other adverse maternal and fetal outcomes.
• IgG1 monoclonal antibodies cross the placenta and can deplete CD38-positive immune cells and decrease bone density. Delay administration of live vaccines in newborns and infants exposed to isatuximab-irfc in the uterus, until blood tests are performed to evaluate immune response.
• Women of pregnancy potential must use effective contraception during treatment and for at least 5 months following the last dose of isatuximab-irfc. If used with pomalidomide, refer additionally to pomalidomide prescribing information for contraception requirement. Isatuximab-irfc and pomalidomide combination should not be used in pregnant women.
• There is no information on the presence of isatuximab-irfc in breastmilk, or its effects on milk production or the breastfed infant. Natural immunoglobulins are present in breastmilk. The effects of local gastrointestinal exposure and limited systemic exposure of isatuximab-irfc in breastfed infants are unknown.
• Nursing mothers should discontinue breastfeeding while on treatment with isatuximab-irfc, because it is administered in combination with pomalidomide and dexamethasone, and because of the potential for serious adverse reactions to these drugs in the breastfed infant.

• You will need regular tests while on treatment with isatuximab-irfc. Follow up with your physician and keep up your appointments.
• Report to your treating physician immediately if you experience:
  • Infusion-related reactions. Symptoms include shortness of breath, wheezing or trouble breathing, swelling of face, mouth, throat, or tongue, throat tightness, palpitations, dizziness, lightheadedness or fainting, headache, cough, rash or itching, nausea, runny or stuffy nose, and/or chills.
  • Fever or other signs of infection.
  • Heart failure symptoms, including cough, trouble breathing, and swelling of legs, ankles, and feet.
• Inform all your healthcare providers that you are being treated with isatuximab-irfc, before receiving blood transfusions.
• Isatuximab-irfc treatment can result in second primary cancer. Inform your physician if you notice any new unusual symptoms or worsening of any existing symptoms.