Isatuximab-irfc (Sarclisa; Sanofi-Aventis) provides patients with another treatment option and significantly reduces the risk of disease progression or death.
Isatuximab-irfc (Sarclisa; Sanofi-Aventis USA, LLC) is a targeted monoclonal antibody that has been approved for use in patients with relapsed and refractory multiple myeloma (the second most common blood cancer).1,2
More than 130,000 Americans have multiple myeloma, and approximately 32,000 patients are diagnosed each year.1 Most patients will relapse because multiple myeloma cannot be cured.3
Indications and dosage
Isatuximab is used in combination with pomalidomide (Pomalyst; Celgene) and dexamethasone (IPd) in patients who have received at least 2 previous treatments, including lenalidomide and proteasome inhibitors.4 Isatuximab can also be used in combination with carfilzomib (Kyprolis; Amgen) and dexamethasone (IKd) in patients who have received 1 to 3 previous treatments.4
The recommended dose of isatuximab is 10 mg/kg (using actual body weight) as an intravenous (IV) infusion.4 Health care professionals perform 4 weeks of infusion every week in cycle 1 (days 1, 8, 15 and 22), and then every 2 weeks in cycle 2 (days 1, 15 and beyond). Until the disease progresses or unacceptable toxicity occurs.4 The first 2 infusions will take 3 to 4 hours, but the remaining infusions will take approximately 75 minutes.2
Isatuximab has 3 functions:2,5
- Discover and bind to the cell surface protein CD38 (widely expressed on myeloma cells), exposing them to be eliminated by the immune system.
- Strengthen the immune system and make it more difficult for myeloma cells to survive.
- Kill myeloma cells directly.
The FDA approved IPd for the first time in March 2020 based on data from the Phase 3 clinical trial ICARIA-MM.2,4 Progression-free survival (PFS) is the main efficacy indicator.2 Researchers found that the risk of disease progression or death was reduced by 40% (p = 00010).1,2
The second approval in March 2021 is based on the efficacy and safety test of IKEMA using IKd.3,4 Researchers found that the risk of disease progression or death was reduced by 45% (p = 0.0032).3,4
Adverse Reaction (AE)
The most common AEs are neutropenia, upper respiratory tract infections (including pneumonia), infusion reactions, and diarrhea.2,4
Health care providers regularly monitor neutrophil counts, and providers may give granulocyte colony stimulating factors to increase white blood cell production.2 Antibiotics or antiviral drugs can help prevent infection.1
The provider manages infusion-related reactions through pre-administration of dexamethasone, acetaminophen, and H2 Antagonists and diphenhydramine (see Table 1).4
The pre-dose is given 15 to 60 minutes before the start of isatuximab infusion.4 The reaction may require a healthcare professional to slow down or stop the infusion, or completely discontinue Etuximab treatment.1
Patients need to drink enough water to prevent dehydration caused by diarrhea.2 The American Society of Clinical Oncology recommends that patients undergoing cancer treatment drink at least 8 glasses of water a day.6
Common AEs unique to IKd include fatigue, hypertension, dyspnea, insomnia, bronchitis, cough, and back pain.4
In addition, patients treated with isatuximab are at risk of new primary cancers (total incidence rate is 3.6%).4 Patients may experience heart failure during IKd treatment.4 Changes in blood tests may affect blood type results.4
Isatuximab binds to CD38 on red blood cells (RBC) and may result in a false positive indirect antiglobulin test (indirect Coombs test). Blood banks can use dithiothreitol-treated RBCs to solve this interference with blood compatibility testing.4
Pregnancy and breastfeeding
Isatuximab is contraindicated in pregnant women and may cause harm to the fetus.4 Women who are breastfeeding should not breastfeed during treatment.4 Pharmacists should advise female patients of childbearing age to take contraceptive measures during treatment and at least 5 months after the last dose.4
1. FDA approved Sarclisa (isatuximab-irfc) for patients with relapsed multiple myeloma [News release]. Sanofi-Aventis USA LLC. March 2, 2020. Visited on July 16, 2021. https://www.sanofi.com/en/media-room/press-releases/2020/2020-03-02-19-51-16
2. Learn about SARCLISA. International Myeloma Foundation. Released in June 2020. Visited on July 15, 2021. https://imf-d8-prod.s3.us-west-1.wasabisys.com/2020-06/U-Sarclisa.pdf
3. FDA approved Sarclisa (isatuximab) combined with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma [News release]. Sanofi-Aventis USA LLC. March 31, 2021. Visited on July 16, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-03-31-23-15-00-2202919
4. Saklissa. Prescription information. Sanofi-Aventis USA LLC; 2021. Visited on July 15, 2021.
5. How Sarclisa works. Sanofi-Aventis USA LLC. Updated in June 2021. Visited on July 16, 2021. https://www.sarclisa.com/how-sarclisa-works
6. The importance of hydrating. American Society of Clinical Oncology (ASCO). July 1, 2009. Visited on July 17, 2021. https://www.cancer.net/blog/podcasts/importance-hydration