Sarclisa (isatuximab-irfc)

What Is Sarclisa?

SARCLISA® is a monoclonal antibody that binds to the CD38 (cluster of differentiation 38) receptor on the surface of myeloma cells. The CD systemis designed to classify more than 200 proteins that can be expressed on (stick out of) the surface of a cell.  

CD38 is widely expressed on the surface of myeloma cells but is only expressed at low levels on the surface of other cells. Sarclisa is a targeted anti-myeloma therapy that binds to and kills myeloma cells directly. It also recruits surrounding immune cells to enhance its myeloma-killing process. 

How Does Sarclisa Work?

Sarclisa works in three distinct ways to reduce the number of myeloma cells in your body: 

• It finds and binds to myeloma cells and exposes them for elimination by your immune system. 
• It helps boost your immune system, making it harder for myeloma cells to survive. 
• It directly kills myeloma cells. 

Who is a Candidate for Sarclisa?

• The FDA has approved Sarclisa for the treatment of adult patients with relapsed or refractory myeloma as part of the following combination therapies:  
  • In combination with the immunomodulatory agent Pomalyst® (pomalidomide) and the steroid dexamethasone [Isa-Pd] for patients who have received at least 2 prior therapies, including the immunomodulatory agent Revlimid® (lenalidomide) and a proteasome inhibitor, such as Velcade® (bortezomib), Ninlaro® (ixazomib), or Kyprolis® (carfilzomib). 
  • In combination with Kyprolis and dexamethasone [Isa-Kd] for patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy. 
• According to a September 20, 2024, press release, the U.S. Food and Drug Administration (FDA) has "approved isatuximab-irfc (Sarclisa, Sanofi-Aventis U.S. LLC) with bortezomib, lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)."
  • This approval was based on results of the phase III IMROZ clinical trial (NCT03319667). The IMROZ trial showed that when Sarclisa is added to Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (VRd) in newly diagnosed multiple myeloma (NDMM) patients who are not eligible for autologous stem cell transplant (ASCT), these patients experienced longer progression-free survival (PFS) compared to those who received VRd-alone. (VRd is the standard of care in newly diagnosed patients who cannot undergo ASCT.) 

How Is Sarclisa Administered?

Sarclisa is administered by intravenous (IV, or through the vein) infusion. 

What Are the Dose and Schedule of Sarclisa Regimens?

Two different combinations are approved for administering Sarclisa.  

The Isa-Pd regimen 

1. Sarclisa (isatuximab-irfc), pomalidomide, and dexamethasone combination therapy, or Isa-Pd 

In this combination, Sarclisa is given as an intravenous (IV) infusion at a dose of 10 mg/kg once-weekly for the first 4 weeks, then once every other week.  

• The first infusion takes about 3–4 hours. 
• The second infusion is about 2 hours. 
• The subsequent infusions are typically 75 minutes 

In addition,  

• Pomalyst is taken by mouth in capsule form at a dose of 4 mg on days 1–21 of every 28-day cycle.  
• Dexamethasone can be taken by mouth or as an IV infusion at a dose of 40 mg once-weekly, or at 20 mg once-weekly for patients over 75 years of age.   

The Isa-Kd regimen

2. Sarclisa (isatuximab-irfc), Kyprolis, and dexamethasone combination therapy, or Isa-Kd 

In this combination, Sarclisa is given as an IV infusion at a dose of 10 mg/kg once-weekly for the first 4 weeks, then once every other week.  

• The first infusion takes about 3–4 hours.
• The second infusion is about 2 hours.
• The subsequent infusions are typically 75 minutes. 

In addition,

• Kyprolis is administered as a once-weekly IV infusion at a dose of 20 mg/m² in the first cycle. 
• During subsquent cycles, Kyprolis is administered once every other week at 56 mg/m². 
• Dexamethasone is administered on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle at a dose of 20 mg. It is given as an IV infusion on days of Sarclisa and/or Kyprolis and taken orally by tablet on other days.  

What Are Possible Side Effects of Sarclisa?

Possible side effects of Isa-Pd: 

Based on data from the ICARIA-MM clinical trial, the most common side effects occurring in 20% or more of patients include the following: 

• upper respiratory tract infection 
• infusion-related reactions 
• pneumonia 
• diarrhea 

The most common hematology laboratory abnormalities occurring in 80% or more of patients include the following:

• decreased levels of hemoglobin 
• decreased levels of neutrophils 
• decreased levels of lymphocytes
• decreased levels of platelets 

Possible serious side effects include the following: 

• pneumonia (26%) 
• upper respiratory tract infections (7%) 
• febrile neutropenia (7%).  

Reported fatal adverse events occurring in more than 1% of patients are pneumonia and other infections (3%). 

Neutropenia 

Neutrophils, the most abundant type of white blood cell (WBC), are the body’s “first responders” in fighting infections. Having too few neutrophils can increase the risk of infection. Approximately 85% of the patients in the Isa-Pd arm of the ICARIA-MM clinical trial had severe neutropenia. Yet, 70.1% of the patients had severe neutropenia in the Pd arm. Neutropenia was the most frequently reported adverse event. 

Prevention and treatment of neutropenia 

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 colony-stimulating factor (CSF) to increase production of your white blood cells. 

Infection

Severe or life-threatening infections occurred in 42.8% of the patients in the Isa-Pd arm of the ICARIA-MM clinical trial versus 30.2% in the Pd arm. 

The most commonly reported infections were upper respiratory, including pneumonia. Immediately contact your doctor or healthcare team if you are showing any signs or symptoms of infection, including the following: 

• fever 
• flu-like symptoms (body aches, sweating, chills) 
• sore throat 
• cough 
• shortness of breath 
• chest pain when you breathe or cough

Prevention and treatment of infection 

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-related reaction 

An infusion-related reaction (IRR) can occur with many IV-administered cancer therapies. Cytokines cause IRR. Cytokines are small proteins released from cells targeted by the monoclonal antibody that affect the behavior of other cells and from immune cells recruited to the area. 

Reactions are often flu-like and may include: 

• nasal congestion 
• fever 
• chills 
• cough 
• throat irritation 
• shortness of breath 
• low blood pressure 
• nausea 
• rash 

IRR occurred in 38.2% of the patients in the Isa-Pd arm of the ICARIA-MM clinical trial. Yet, only 2.6% of those cases were severe. The majority of IRRs were during the first dose. 

Prevention and treatment of IRR 

Medications are given before and during Sarclisa infusions to minimize the risk of IRR. If a reaction of any kind occurs during your infusion of Sarclisa, the infusion will be stopped. 

Possible side effects of Isa-Kd 

Based on data from the IKEMA clinical trial, the most common side effects occurring in 20% or more of patients include the following: 

• upper respiratory tract infection 
• infusion-related reaction (IRR)
• fatigue 
• hypertension 
• diarrhea 
• pneumonia 
• shortness of breath 
• insomnia 
• bronchitis 
• cough 
• back pain

The most common hematology laboratory abnormalities include decreased levels of hemoglobin, lymphocytes, and platelets.  

Reported fatal adverse reactions that occurred in more than 1% of patients during treatment were pneumonia (1.7%) and cardiac failure (1.1%). 

Serious treatment-emergent adverse events (TEAEs) were reported in 70.1% of the patients in the Isa-Kd arm vs. 59.8% in the Kd arm of the IKEMA clinical trial. 

The most common, any Grade, non-hematologic TEAEs with Isa-Kd were the following: 

• infusion-related reaction (45.8%) 
• diarrhea (39.5%) 
• hypertension (37.9%) 
• upper respiratory tract infection (37.3%)

Infusion-related reaction 

An infusion-related reaction (IRR) can occur with many IV-administered cancer therapies. Cytokines cause IRR. Cytokines are small proteins released from cells targeted by the monoclonal antibody to affect the behavior of other cells and from immune cells recruited to the area. 

Reactions are often flu-like, and include the following: 

• nasal congestion 
• fever 
• chills 
• cough 
• throat irritation 
• shortness of breath 
• low blood pressure 
• nausea 
• rash 

IRR occurred in 46% of the patients in the Isa-Kd arm of the IKEMA clinical trial. Yet, only 0.6% were Grade 3, and none were Grade 4. The occurrence of IRR in the Kd arm was 3.3%, and none were Grade 3 or 4. 

Prevention and treatment of IRR 

Medications are given before and during Sarclisa infusions to minimize the risk of IRR. If a reaction of any kind occurs during your infusion of Sarclisa, the infusion will be stopped. 

Diarrhea 

Diarrhea is defined as 3 or more loose stools per day. Severe diarrhea is defined as 7 or more loose stools per day requiring treatment with IV fluids or hospitalization. Diarrhea occurred in 36% of the patients in the Isa-Kd arm versus 29% in the Kd arm of the IKEMA clinical trial.  

Grade 3 diarrhea was noted in 2.8% vs. 2.5% of patients, respectively. No Grade 4 cases were reported. 

Prevention and treatment of diarrhea 

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 if you experience any of the following: 

• dizziness 
• light-headedness 
• fainting
• Your doctor may administer medication or IV hydration

Hypertension 

Hypertension (HTN) is a medical condition in which the blood pressure (BP) in the arteries is elevated. It is also known as high blood pressure (HBP). HTN occurred in 37% of the patients in the Isa-Kd arm versus 32% in the Kd arm of the IKEMA clinical trial. 

Prevention and treatment of hypertension 

If you have HTN before starting treatment with Kyprolis, your doctor should optimize the treatment of your HTN in advance. Monitor BP carefully when receiving your myeloma therapy, especially during the first month. If very high BP or complications develop, report this to your doctor immediately. Your doctor will determine if your medication should be reduced, interrupted, or discontinued. 

Infection 

Upper respiratory tract infection occurred in 67% of patients in the Isa-Kd arm versus 57% in the Kd arm of the IKEMA clinical trial. Pneumonia occurred in 36% of patients on Isa-Kd versus 30% on Kd. Bronchitis occurred in 24% of patients on Isa-Kd vs. 13% on Kd. 

Immediately contact your doctor or healthcare team 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 

Prevention and treatment of infection 

You must report your symptoms to your doctor, who will guide you in managing these symptoms. If you develop an infection, the doses of your medications may be reduced, interrupted, or discontinued. 

Fatigue 

Fatigue caused by cancer or cancer treatment is a distressing, persistent, subjective sense of tiredness or exhaustion that is not proportional to recent activity and interferes with usual functioning. Fatigue that is related to cancer and its treatments is different from – and more severe than – normal fatigue. It tends to last longer and includes the feeling of overall weakness. 

Fatigue occurred in 42% of the patients in the Isa-Kd arm vs. 32% in the Kd arm of the IKEMA clinical trial. Grade 3 fatigue was 5% vs. 3.3%, respectively. No Grade 4 cases were reported in either study arm. 

Prevention and treatment of fatigue 

The effects of fatigue may be minimized by maintaining the following: 

• a moderate level of activity 
• a healthy diet and proper fluid intake 
• a consistent sleeping schedule 
• regularly scheduled visits with your doctor to monitor your red blood cell count (low red blood cells, or anemia, can cause fatigue) and to discuss issues that may contribute to your fatigue 
• a careful review of the side effects of any other medications you take to ensure that they do not contribute to your fatigue

Learn more on managing fatigue in the IMF Publication Understanding Fatigue. 

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 https://www.sanoficareassist.com/sarclisa/.