- Multiple myeloma in patients who have received ≥2 prior therapies including lenalidomide and a proteasome inhibitor (in combination with pomalidomide and dexamethasone).
- Relapsed or refractory multiple myeloma in patients who have received 1–3 prior lines of therapy (in combination with carfilzomib and dexamethasone).
Binds to CD38 on tumor cells causing apoptosis, thereby inhibiting growth of CD38-expressing tumor cells.
Improved progression-free survival.
Absorption: IV administration results in complete bioavailability.
Distribution: Minimally distributed to extravascular tissues.
Metabolism and Excretion: Metabolized into small peptides by catabolic pathways.
TIME/ACTION PROFILE (plasma concentrations)
|IV||unknown||end of infusion||unknown|
- Severe hypersensitivity
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Rep: Women of reproductive potential
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
GI: diarrhea, nausea, vomiting
Hemat: NEUTROPENIA, anemia, lymphopenia, thrombocytopenia
Resp: dyspnea, pneumonia, upper respiratory tract infection
Misc: INFECTION, INFUSION REACTIONS (including anaphylaxis and angioedema), secondary malignancy (primarily skin cancers)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
IV (Adults): Cycle 1– 10 mg/kg on Days 1, 8, 15, and 22 of the 28–day cycle. Cycle 2 and beyond– 10 mg/kg on Days 1 and 15 of each 28–day cycle; continue until disease progression or unacceptable toxicity.
Solution for injection: 20 mg/mL
- Monitor vital signs frequently and assess for signs and symptoms of infusion-related reactions (dyspnea, cough, chills, nausea, hypertension) during infusion; usually occur during 1st infusion. Signs and symptoms of severe reactions (cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, swelling) may occur. Premedicate to decrease risk and severity of reactions. For ≥Grade 2 reactions, hold isatuximab and treat symptomatically. If symptoms improve to <1, resume infusion at half of infusion rate and monitor closely. If symptoms do not recur after 30 min, increase infusion rate to initial rate, and then increase incrementally. If symptoms do not improve to Grade ≤1, persist or worsen despite medications, or require hospitalization, permanently discontinue therapy. For ≥Grade 4 or anaphylactic reactions, discontinue isatuximab permanently and treat symptomatically.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
Conduct blood type and screen test, and possible phenotyping, before starting therapy. May cause interfere with blood bank serologic tests with false positive indirect antiglobulin test (indirect Coombs test), antibody detection (screening) tests, antibody identification panels, and antihuman globulin crossmatches. Blood transfusions in these patients were administered without hemolysis.
- Frequently causes neutropenia and febrile neutropenia. Monitor CBC periodically during therapy. Antibiotics and antiviral prophylaxis may be considered. Monitor patients with neutropenia for signs of infection. If Grade 4 neutropenia occurs, hold dose until neutrophil count recovery to ≥1.0 × 109 /L and provide supportive care with growth factors. No dose reductions are recommended.
- Administer pre-medications 15–60 min before infusion: dexamethasone 40 mg PO or IV (20 mg for patients ≥75 years), acetaminophen 650–1000 mg PO, H2 antagonists, diphenhydramine 25–50 PO or IV (IV route preferred for first 4 infusions).
- If a planned dose is missed, administer dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval.
- IV Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers.
- Intermittent Infusion: Dilution: Remove volume equal to volume of isatuximab dose from 250 mL bag of 0.9% NaCl or D5W diluent. Add isatuximab dose to bag to dilute. Mix by gently inverting; do not shake. Solution is slightly opalescent, colorless to slightly yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Infusion bag must be made of polyolefins (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) with di-(2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate (EVA). Use diluted solution 48 hr if refrigerated, followed by 8 hr, including infusion time, at room temperature.
- Rate: Infuse through tubing of PE, PVC with or without DEHP, polybutadiene [PBD], or polyurethane [PU] with a 0.22 micron in-line filter (polyethersulfone [PES], polysulfone, or nylon). For 1st infusion, infuse at 25 mL/hr for 60 min; if no infusion-related reactions, increase rate by 25 mL/hr every 30 min to a maximum of 150 mL/hr. For 2nd infusion, infuse at 50 mL/hr for 30 min; if no infusion-related reactions, increase rate by 50 mL/hr for 30 min then increase by 100 mL/hr every 30 min to a maximum of 200 mL/hr. For subsequent infusions, infuse at 200 mL/hr.
- Y-Site Incompatibility: Do not infuse with other agents in same line.
- Explain purpose of isatuximab to patient. Advise patient to read Patient Information before starting and periodically during therapy in case of changes.
- Advise patient to notify health care professional if signs and symptoms of infusion-related reactions (feeling short of breath, cough, chills, nausea) occur within 24 hrs of start of infusion.
- Instruct patient to notify health care professional promptly signs and symptoms of infection (fever, sore throat, lower back or side pain, difficult or painful urination) occur. Caution patient to avoid crowds and persons with known infections.
- Inform patient of potential for development of second primary malignancies. Advise patients to maintain regular exams for skin cancer.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Instruct patient to notify health care professional of therapy in case red blood cell transfusion is planned.
- Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception for at least 5 mo after last dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Hold the administration of live vaccines to neonates and infants exposed to isatuximab in utero until a hematology evaluation is completed.
Improved progression-free survival in multiple myeloma.