What Is Sarclisa?
Sarclisa is a novel anti-CD38 monoclonal antibody. Although antibodies are a naturally-occurring part of the immune system, Sarclisa and other antibodies used to treat diseases are made in a laboratory. A laboratory-made antibody is designed to function like a naturally-occurring antibody, and to bind to a specific single protein on the surface of the targeted cells (in this case, myeloma cells). In this sense, Sarclisa is a targeted anti-myeloma therapy.
How Does Sarclisa Work?
Sarclisa binds to the cell-surface protein CD38 (cluster of differentiation 38) on myeloma cells. The CD system is a way to classify more than 200 proteins that stick out of cells (e.g., CD1, CD2, CD3). CD38 is widely expressed on the surface of myeloma cells, but is only expressed at low levels on other cells, so the drug is specific to the myeloma cells and not the good cells around it. When Sarclisa binds to myeloma cells, it not only kills myeloma cells directly, but also recruits other immune system cells to kill myeloma cells.
Who is a Candidate for Sarclisa?
In March 2020, the U.S. Food and Drug Administration (FDA) approved Sarclisa in combination with the immunomodulatory drug Pomalyst® (pomalidomide) and the steroid dexamethasone for patients with relapsed refractory myeloma who have received at least two therapies that included Revlimid® (lenalidomide) and a proteasome inhibitor (such as Velcade®, Ninlaro®, or Kyprolis®). The number of “lines” of therapy is not defined, so as long as patients have had Revlimid and a proteasome inhibitor – and are currently relapsing – they are eligible. This is the same eligibility criteria for receiving Pomalyst + dexamethasone (Pd) alone.
How Is Sarclisa Administered?
The FDA approval of Sarclisa was based on data from the ICARIA-MM phase III clinical trial, which compared Sarclisa combined with Pomalyst and dexamethasone (Isa-Pd) to Pomalyst and dexamethasone alone (Pd). Adding Sarclisa to Pd improved progression-free survival in both standard-risk patients and those with high-risk myeloma, which was defined in the ICARIA-MM clinical trial as myeloma with one or more of these chromosomal abnormalities: del(17p), t(4;14), or t(14;16). Therefore, Sarcilisa is administered as part of a three-drug regimen known as Isa-Pd, or Sarclisa plus Pomalyst and dexemthasone.
What Are the Dose and Schedule of Isa-Pd?
The standard doses and schedules of the drugs in the Isa-Pd regimen are:
- Sarclisa is given as an intravenous (IV, into a vein) infusion at a dose of 10 mg/kg every week for 4 weeks, then every 2 weeks. The first and second infusions take about 3–4 hours, but the remaining infusions are typically 75 minutes.
- Pomalyst is taken by mouth in capsule form, 4 mg on days 1–21 of every 28-day cycle.
- Dexamethasone can be taken by mouth in tablet form or as an IV infusion, 40 mg once weekly, and for patients over 75 years of age, 20 mg once weekly.
The Isa-Pd regimen is given until disease progression or unacceptable toxicity.
What Are Possible Side Effects of the Isa-Pd regimen?
- Neutropenia (See Myelosuppression for details.)
Your neutrophil count will be monitored frequently while you are receiving treatment with Isa-Pd. The doses of your medications may be interrupted and/or lowered if your neutrophils are too low. Your doctor may also give you a granulocyte colony-stimulating factor (G-CSF) to increase production of your white blood cells.
- Infection
The most commonly reported infections were upper respiratory, including pneumonia. You must call your doctor immediately (or go to the emergency room if your doctor is unavailable), if you are showing any signs or symptoms of infection, including:
- Fever
- Flu-like symptoms (body aches, sweating, chills)
- Sore throat
- Cough
- Shortness of breath
- Chest pain when you breathe or cough
You must report your symptoms to your doctor, who will determine how they should be managed and if you need to receive an antibiotic, or other medications. If you develop an infection, the doses of your medications may be interrupted and/or lowered.
- Infusion reaction
Infusion reactions can occur with many IV-administered cancer therapies. Infusion reactions to monoclonal antibodies are caused by the release of cytokines, small proteins released by cells in order to affect the behavior of other cells. Infusion reactions result both from the release of cytokines from cells targeted by the monoclonal antibody and from immune system cells that are recruited to the area. Reactions are often flu-like, and include nasal congestion, fever, chills, cough, throat irritation, shortness of breath, low blood pressure, nausea, and rash.
To minimize the risk of infusion reactions, medications are given before and during Sarclisa infusions. If a reaction of any kind occurs during your infusion of Sarclisa, the infusion will be stopped
- Diarrhea (See Gastrointestinal Problems for details.)
Diarrhea might occur while taking Sarclisa, causing dehydration. Precautions should be taken to prevent dehydration caused by either excessive or persistent diarrhea. Be sure to drink a sufficient amount of water. Contact your doctor and/or nurse for medical advice if you experience dizziness, light-headedness, and/or fainting. Your doctor may administer antidiarrheal medication or IV hydration, as required.
Access to Sarclisa and Other Resources
CareAssist by Sanofi Genzyme helps eligible patients with access and support for Sarclisa. To explore the services and resources that may be available for you, please call 1.833.930.2273 or visit SanofiCareAssist.com/Sarclisa.
