Isatuximab-irfc (Sarclisa) for relapsed / refractory multiple myeloma

Isatuximab-irfc (Sarclisa; sanofi-aventis) offers patients another treatment option and significantly reduces the risk of disease progression or death.

Isatuximab-irfc (Sarclisa; sanofi-aventis US LLC) is a targeted monoclonal antibody approved for patients with relapsed and refractory multiple myeloma, the second most common cancer of the blood.1.2

More than 130,000 Americans are affected by multiple myeloma and approximately 32,000 patients are diagnosed each year.1 Most patients will relapse because the multiple myeloma is incurable.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 a proteasome inhibitor.4 Isatuximab is also indicated in combination with carfilzomib (Kyprolis; Amgen) and dexamethasone (IKd) in patients who have received 1 to 3 previous lines of treatment.4

The recommended dose of isatuximab is 10 mg / kg, using actual body weight, as an intravenous (IV) infusion.4 Healthcare professionals give the infusion weekly for 4 weeks in cycle 1 (days 1, 8, 15 and 22), then every 2 weeks in cycle 2 (days 1, 15 and beyond), until ‘to disease progression or unacceptable toxicity.4 The first 2 infusions last 3 to 4 hours, but the remaining infusions last approximately 75 minutes.2

Action mechanism

Isatuximab works in 3 ways:2.5

  1. Finds and binds to cell surface protein CD38 (widely expressed on myeloma cells), exposing them to elimination by the immune system.
  2. Strengthens the immune system, which makes it harder for myeloma cells to survive.
  3. Directly kills myeloma cells.

FDA approval

The FDA first approved IPd in ​​March 2020 based on data from the ICARIA-MM Phase 3 clinical trial.2.4 Progression-free survival (PFS) was the main measure of effectiveness.2 The researchers found a 40% reduction in the risk of disease progression or death (p = 00010).1.2

The second approval in March 2021 was based on IKEMA’s efficacy and safety trial using IKd.3.4 The researchers found a 45% reduction in the risk of disease progression or death (p = 0.0032).3.4

Adverse reactions (AEs)

The most common AEs are neutropenia, upper respiratory tract infections (including pneumonia), infusion-related reactions, and diarrhea.2.4

Healthcare providers periodically monitor neutrophil counts and may give granulocyte colony stimulating factor to increase white blood cell production.2 Antibiotics or antivirals can help prevent infection.1

Providers manage infusion reactions with premedication using dexamethasone, acetaminophen, H2 antagonists and diphenhydramine (see Table 1).4

Premedications are given 15 to 60 minutes before the start of the isatuximab infusion.4 Reactions may require healthcare professionals to slow or stop the infusion, or to stop treatment with isatuximab completely.1

Patients should prevent dehydration caused by diarrhea by drinking enough water.2 The American Society of Clinical Oncology recommends that patients receiving cancer treatment drink at least 8 cups of water each day.6

Unique to IKd, common AEs include fatigue, hypertension, dyspnea, insomnia, bronchitis, cough, and back pain.4

In addition, patients treated with isatuximab are at risk of new primary cancers (the overall incidence is 3.6%).4 Patients may develop heart failure during treatment with IKd.4 Changes in blood tests can occur and affect blood group results.4

Isatuximab binds to CD38 on red blood cells (RBCs) and may result in a false positive indirect antiglobulin test (indirect Coombs test). Blood banks can resolve this interference with blood compatibility tests by using red blood cells treated with dithiothreitol.4

Pregnancy and breast feeding

Isatuximab is contraindicated in pregnant women and may harm the unborn child.4 Breast-feeding women should not breast-feed during treatment.4 Pharmacists should advise patients of childbearing potential to use contraception during treatment and for at least 5 months after the last dose.4

THE REFERENCES

1. FDA approves Sarclisa (isatuximab-irfc) for patients with relapsed multiple myeloma [News release]. sanofi-aventis US LLC. March 2, 2020. Accessed July 16, 2021. https://www.sanofi.com/en/media-room/press-releases/2020/2020-03-02-19-51-16

2. Understand the SARCLISE. International Myeloma Foundation. Published June 2020. Accessed July 15, 2021. https://imf-d8-prod.s3.us-west-1.wasabisys.com/2020-06/U-Sarclisa.pdf

3. FDA approves Sarclisa (isatuximab) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma [News release]. sanofi-aventis US LLC. March 31, 2021. Accessed July 16, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-03-31-23-15-00-2202919

4. Sarclisa. Prescribing information. sanofi-aventis US LLC; 2021. Accessed July 15, 2021.

5. How does Sarclisa work. sanofi-aventis US LLC. Updated June 2021. Accessed July 16, 2021. https://www.sarclisa.com/how-sarclisa-works

6. The importance of hydration. American Society for Clinical Oncology (ASCO). July 1, 2009. Accessed July 17, 2021. https://www.cancer.net/blog/podcasts/importance-hydration

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About Hector Hedgepeth

Hector Hedgepeth

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