Written by: Jon Suyko Pharm.D., BCPS UCHealth Highlands Ranch
The purpose of this PQI is to discuss the option of using isatuximab-irfc (Sarclisa®) for multiple myeloma patients who have been refractory to two prior treatment therapies including treatment with lenalidomide and a protease inhibitor.
Isatuximab-irfc is an intravenous infused monoclonal antibody which selectively binds to the CD38 glycoprotein found on the surface of malignant plasma cells. Isatuximab-irfc has multiple mechanisms of action.
ICARIA-MM was a phase 3 trial which compared the regimen of isatuximab-irfc plus pomalidomide and low dose dexamethasone to pomalidomide plus low dose dexamethasone alone in patients who received two or more prior treatment therapies and had failed lenalidomide and a proteasome inhibitor3. The triplet therapy of isatuximab-irfc plus pomalidomide and low dose dexamethasone reduced the risk of disease progression or death by 40% compared to pomalidomide plus dexamethasone alone4.
- Pre-medication is recommended to reduce risk of infusion reactions5
- Dexamethasone 40mg either oral or IV x 1 dose. If patient is ≥ 75 years then give 20mg.
- Acetaminophen 650-1000mg x 1 dose
- H2 antagonist x 1 dose (Ex: famotidine 20mg)
- Diphenhydramine 25-50mg orally or IV. Note: IV route is preferred for the first four infusions
- Verify dosing of isatuximab-irfc is 10 mg/kg intravenous infusion every week for 4 weeks followed by every 2 weeks in combination with pomalidomide and dexamethasone until disease progression or unacceptable toxicity.
- Dosing is based on patient’s actual body weight at the beginning of each cycle.
- Isatuximab-irfc is available in 100mg/5ml vials and 500mg/25 ml vials
- Review institutional policy to consider using montelukast (usage not required)
- Preparation: isatuximab-irfc is compatible with 0.9% Sodium Chloride (NS) and 5% Dextrose (D5W).
- The infusion bag may be gently swirled to create a homogenous mixture. Do Not Shake.
- The binding of isatuximab-irfx to CD38 of red blood cells may result in a false positive indirect Coombs test.
- Table 1: Rate of infusion for isatuximab-irfc (5)
Volume Initial rate No infusion reaction Rate Increment Maximum Rate First infusion 250 ml 25 ml/hr For 60 minutes 25 ml/hr every 30 minutes 150 ml/hr Second Infusion 250 ml 50 ml/hr For 30 minutes 50 ml/hr for 30 minutes then increase by 100ml/hr every 30 minutes 200 ml/hr Subsequent Infusions 250 ml 200 ml/hr – – 200 ml/hr
Patient Centered Activities:
- Patient Education
- Infusion reactions may occur (38%) with the administration of isatuximab-irfc. These usually occur with the first infusion and in most cases, resolve on the same day. Infusion reactions may include difficulty breathing, cough, chills and nausea and should counsel patient to report systems4
- Counsel patient on neutropenic related systems such as fever. Monitor blood counts during therapy
- Patient should report any symptoms of low grade fever, chills, sweating, sore throat, cough or shortness of breath.
- Sanofi CareASSIST Program6
- Patient’s with commercial or private insurance may be eligible for $0 copay; No income requirement
- Copay covers any product-specific copay, coinsurance, and insurance deductibles up to $25,000 in assistance per year.
- Patient’s are responsible for costs which exceed the $25,000/year maximum benefit.
- CareASSIST not available for Medicare, Medicaid, Veterans Affairs/Department of Defense, TRICARE, or similar federal or state programs.
- Trudel, Suzanne. “Incorporating Isatuximab in the Treatment of Multiple Myeloma.” The Lancet, vol. 394, 7 Dec. 2019, pp. 2045–2046.
- Moreno, Laura, et al. “The Mechanism of Action of the Anti-CD38 Monoclonal Antibody Isatuximab in Multiple Myeloma.” Clinical Cancer Research, vol. 25, no. 10, 15 May 2019.
- Martin, Thomas, et al. “Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab.” Cells, vol. 8, no. 1522, 26 Nov. 2019.
- Attal, Prof. Michael, et al. “Isatuximab plus Pomalidomide and Low-Dose Dexamethasone versus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (ICARIA-MM): a Randomised, Multicentre, Open-Label, Phase 3 Study.” The Lancet, vol. 394, no. 10214, 7 Dec. 2019, pp. 2096–2107.
- Sarclisa®(isatuximab-irfc) Package Insert Revised: 3/2020
- “CareASSIST Copay Program.” Hcp, www.sanoficareassist.com/hcp/sarclisa/copay.