Understanding SARCLISA®
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You are not alone
The International Myeloma Foundation (IMF) is here to help you. The IMF is committed to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and their care partners, friends, and family members.
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What you will learn from this booklet
Myeloma is a cancer that is not known to most patients at the time of diagnosis. If you have myeloma, it is important and helpful for you to learn about your disease, its treatment options, and supportive care measures in order to play an active role in your own medical care and to make good decisions about your care in partnership with your doctor.
If you are a patient with myeloma, we suggest that you read the IMF’s publication, Patient Handbook for Multiple Myeloma, which will help you to better understand this disease. In addition, this booklet will direct you to resources that may be relevant in your particular case. All IMF publications are free-of-charge and can be read, downloaded, or requested in printed format at publications.myeloma.org.
The IMF’s Understanding-series publications address specific drugs, drug classes, and combination therapies used to treat myeloma. These booklets also discuss supportive care measures that may help manage the symptoms and side effects of myeloma and its treatments. The IMF’s publication, Understanding Your Test Results, explains how myeloma is diagnosed, monitored, and assessed throughout the disease course.
Words in bold+blue type are explained in the IMF’s companion publication, Understanding Myeloma Vocabulary, a comprehensive glossary that also can be helpful in discussions with your doctor. Myeloma is complicated, but the language that describes it doesn’t have to be hard to understand.
If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources.
This booklet discusses Sarclisa® (also known as isatuximab-irfc, its generic drug name). The U.S. Food and Drug Administration (FDA) first approved Sarclisa as a treatment for myeloma in 2020.
How Sarclisa works
Sarclisa is a monoclonal antibody that binds to the CD38 (cluster of differentiation 38) receptor on the surface of myeloma cells. The CD system is 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, plus it also recruits surrounding immune cells to enhance its myeloma-killing process.
FDA-approved indications for Sarclisa
The FDA has approved Sarclisa for the treatment of adult patients with myeloma as part of the following combination therapies:
1. Sarclisa + the proteasome inhibitor Velcade® (bortezomib) + the immunomodulatory agent Revlimid® (lenalidomide) + the steroid dexamethasone [Isa-VRd] for adult patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for an autologous stem cell transplant (ASCT).
2. Sarclisa + the proteasome inhibitor Kyprolis® (carfilzomib) + dexamethasone [Isa-Kd] for patients with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior lines of therapy.
3. Sarclisa + the immunomodulatory agent Pomalyst® (pomalidomide) + dexamethasone [Isa-Pd] for patients with RRMM who have received at least 2 prior therapies including Revlimid and a proteasome inhibitor, such as Velcade, Kyprolis, or Ninlaro® (ixazomib).
To learn more about the drugs used in combination with Sarclisa, read the following IMF publications, listed here in alphabetical order:
¡ Understanding Dexamethasone in the Treatment of Myeloma
¡ Understanding KYPROLIS® (carfilzomib)
¡ Understanding POMALYST® (pomalidomide)
¡ Understanding REVLIMID® (lenalidomide)
¡ Understanding VELCADE® (bortezomib)
Clinical trial experience with Sarclisa
Clinical trials are medical research studies with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions.
VRd vs. Isa-VRd
In December 2024, at the annual meeting of the American Society of Hematology (ASH), the final analysis was presented of progression-free survival (PFS) from the first randomization in Part 1 of the GMMG-HD7 phase III clinical trial of VRd vs. Isa-VRd induction therapy for transplanteligible patients with NDMM. Isa-VRd led to deeper minimal residual disease (MRD) -negative response post-transplant when compared with VRd alone. At a median follow-up of 48 months, 18 weeks of Isa-VRd induction therapy – without consolidation therapy – resulted in a 30% reduction in risk of progression or death compared with VRd regardless of which maintenance therapy was received by the patient.
In September 2024, the FDA approval of the Isa-VRd “quadruplet” (4-drug) combination therapy was based on the results of the IMROZ phase III clinical trial, which demonstrated that when Sarclisa is added to VRd in patients with NDMM who are ASCT-ineligible, these patients experienced longer PFS compared to those who received VRd alone. This study evaluated 446 patients who were 80 years of age or younger. An independent review committee assessed PFS efficacy using criteria by the IMF International Myeloma Working Group (IMWG). The median PFS was not reached in the Isa-VRd arm; it was 54.3 months in the VRd arm. In the Isa-VRd arm, 63% of study patients were still in remission at 4 years vs. 45% of patients in the VRd arm. For patients with myeloma, frontline therapy has a long-term effect as the first remission is usually the longest.
KRd vs. Isa-KRd
In December 2023, a plenary session at the ASH annual meeting presented the results from the ISKIA phase III clinical trial of 302 patients with NDMM who were ASCT-eligible. Patients were randomized to two study arms with 151 patients in each arm. One arm received Isa-KRd and and the other arm received KRd alone. The study assessed efficacy and safety of Isa-KRd as pre-ASCT induction therapy and post-ASCT consolidation therapy. The addition of Sarclisa to KRd induction and consolidation therapies significantly increased the rates of MRD-negativity in every treatment phase and with no new safety concerns, including in patients with high-risk multiple myeloma (HRMM).
Pd vs. Isa-Pd
The FDA approval of Sarclisa in 2020 was based on data from the ICARIA-MM phase III clinical trial, which compared Isa-Pd to Pd alone. The study included 307 patients from 96 centers across 24 countries. The main efficacy outcome measure was progression-free survival (PFS) using IMWG criteria. In patients treated with Isa-Pd, the improvement in PFS represented a 40% reduction in
the risk of disease progression or death. Median PFS for the patients in the Isa-Pd study arm was 11.53 months vs. 6.47 months for the patients in the Pd arm. The Isa-Pd regimen consistently prolonged PFS across subgroups, including Revlimid-refractory patients. Adding Sarclisa to Pd improved PFS in both standard-risk patients and those with HRMM, which was defined as myeloma with one or more of these chromosomal abnormalities: del(17p), t(4;14), or t(14;16). Nearly 32% of patients in the Isa-Pd arm had at least a 90% response to therapy (defined as very good partial response [VGPR]), as compared to only 8.5% of the patients in the Pd arm. MRD-negativity occurred in 5.2% of Isa-Pd patients and in 0% of Pd patients.
SQ administration of Sarclisa
In June 2022, results of an interim phase Ib clinical trial of subcutaneous (SQ) injection of Sarclisa by a hands-free on-body delivery system (OBDS) were presented at the annual meeting of the American Society of Clinical Oncology (ASCO). This study of the Isa-Pd regimen in patients with RRMM demonstrated that SQ administration of Sarclisa by OBDS has a safety profile consistent with intravenous (IV) infusion of Sarclisa. Efficacy in the SQ cohort was comparable to the results of the ICARIA-MM phase III clinical trial. At this time, SQ administration of Sarclisa is not approved by the FDA.
Finding a clinical trial to match your needs
The IMF has partnered with SparkCures to help myeloma patients discover and explore clinical trials across the U.S. that best match their needs. To identify a clinical trial personalized to your preferences, visit myeloma.org/sparkcures or contact the IMF InfoLine. For information about all clinical trials with Sarclisa in various myeloma disease settings and drug combinations, you can also visit clinicaltrials.gov.
Warnings and precautions
Safety precautions must be exercised with the use of Sarclisa. Before starting treatment with Sarclisa, be sure to have a comprehensive discussion of your treatment options with your doctor. Tell your doctor about all of your medical conditions, especially heart problems. Be sure to disclose all the medicines you take, including over-the-counter (OTC) drugs.
Infusion-Related Reaction (IRR)
Serious IRRs, including life-threatening anaphylactic reactions, have occurred with Sarclisa treatment in less than 1% of patients who participated in the ICARIA-MM, IKEMA, and IMROZ clinical trials. Signs and symptoms may include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling. In clinical trials with Sarclisa, IRRs were related to treatment discontinuation in 1% of patients.
IRR can occur with many IV-administered cancer therapies. IRR is caused by cytokines, small proteins released from cells targeted by the monoclonal antibody in order to affect the behavior of other cells, and also from immune 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.
Prevention and treatment of IRR
To decrease the risk and severity of IRRs, patients are given medication before and/or during Sarclisa infusions. Medications may include acetaminophen, H2 antagonists, diphenhydramine or equivalent, and/or dexamethasone. If an IRR occurs, the infusion may be stopped.
Infection
Sarclisa can cause severe, life-threatening, or fatal infections. In the abovecited clinical trials, serious infections occurred in 46% of study patients who received Sarclisa at the recommended dose, Grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia, which occurred in 32% of study patients. Immediately contact your doctor if you experience any signs or symptoms of infection, including the following:
¡ Fever, ¡ Shortness of breath,
¡ Sore throat, ¡ Flu-like symptoms (body aches, sweating, chills),
¡ Cough, ¡ Chest pain when you breathe or cough.
Prevention and treatment of infection
To decrease the risk and severity of infections, you may be given prophylactic medication in accordance with guidelines. You must report any signs or symptoms of infection to your doctor, who will determine how they should be managed.
Neutropenia
Neutropenia is a reduced level of neutrophils, which can lead to infection caused by bacteria or fungi. Neutropenia occurred in 81% of patients who received Sarclisa in the above-cited clinical trials, with Grade 3 or 4 in 52% of study patients. Fever is the most common sign of neutropenia. If you develop a fever, you must get immediate medical attention.
Prevention and treatment of neutropenia
Your neutrophil count will be monitored while you receive treatment with Sarclisa. If your doctor determines that the level of your neutrophils is low, your doses of Sarclisa may be decreased or interrupted. You may also receive a colony-stimulating factor (CSF) to increase your white blood cell (WBC) production.
Second primary malignancy (SPM)
In the above-cited clinical trials, the incidence of SPMs was increased in patients treated with Sarclisa, occurring in 12% of study patients. The most common SPMs that occurred in 1% or more of study patients included skin cancers and solid tumors (other than skin cancers).
Laboratory test interference
The use of Sarclisa may interfere with the following laboratory tests:
¡ Sarclisa may interfere with serological testing and may result in a false-positive indirect antiglobulin test. Patients are tested for blood type before their first infusion of Sarclisa. Interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non-cross-matched ABO/RhDcompatible RBCs can be given as per local blood bank practices.
¡ Sarclisa may interfere with serum protein electrophoresis (SPEP) and immunofixation (IFE) tests used to monitor M-protein. This can impact the accuracy of the determination of complete response (CR) in some patients with IgG kappa myeloma protein.
Embryo-fetal toxicity
The mechanism of action (MOA) of Sarclisa can cause fetal harm. Female patients of reproductive potential must use an effective method of contraception during treatment with Sarclisa and for 5 months after the last dose of Sarclisa.
Due to the potential for harm in the breastfed child, lactating women should not breastfeed during treatment with Sarclisa.
Possible common side effects of Sarclisa
Anemia (low red blood cell count)
Red blood cells contain hemoglobin, a protein that carries oxygen to the body’s tissues and organs. Anemia is usually defined as a decrease in hemoglobin < 10 g/dL or as a decrease of ≥ 2 g/dL from the normal level for an individual. More than 13–14 g/dL is considered normal. Low levels of oxygen in the body may cause shortness of breath and feelings of exhaustion.
Prevention and treatment of anemia
Your healthcare providers will determine which treatment regimen for anemia is best suited to your needs and safest for you. The following are options for treatment of anemia:
¡ Adjusting medications.
¡ Blood transfusions.
¡ Erythropoietic (red blood cell-making) agents.
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.
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 dizziness, light-headedness, and/or fainting. Your doctor may administer medication or IV hydration.
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.
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, and
¡ A careful review of the side effects of any other medications you are taking to ensure that they are not contributing to your fatigue.
For more information about this side effect, read the IMF’s publication Understanding Fatigue.
Hypertension
Hypertension (HTN) is a medical condition in which the blood pressure (BP) in the arteries is elevated; also known as high blood pressure (HBP).
Prevention and treatment of hypertension
If you have HTN prior to starting treatment with Kyprolis, your doctor should optimize 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.
Thrombocytopenia (low number of platelets)
Thrombocytopenia is a low number of thrombocytes (platelets) in the blood. Please note that the “normal” level of platelets may vary from one laboratory to another. For example, at Mayo Clinic the “normal” level is ≥ 150,000 platelets per microliter of circulating blood. If the platelet count is less than 50,000, bleeding problems may occur. Major bleeding is usually associated with a reduction in count to less than 10,000 platelets.
Prevention and treatment of thrombocytopenia
Due to the possibility of thrombocytopenia during treatment with Sarclisa, your doctor will monitor your blood cell counts. Promptly inform your doctor if you experience excessive bruising or bleeding.
Treatment for low platelet count depends on the severity of the condition. Mild thrombocytopenia might not require treatment. At the discretion of your doctor, management of thrombocytopenia may include medication or platelet transfusion.
Upper respiratory tract infection
Upper respiratory tract infections can be a bacterial or viral infection of the nose, throat, sinuses, or larynx.
Prevention and treatment of upper
respiratory tract infection
Report your symptoms to your doctor immediately. If your infection is serious and your white blood cell count is low, the doctor may hold your Sarclisa infusion until you recover or support you with medications to stimulate the production of new white blood cells.
Other possible side effects
Possible common side effects of treatment with Sarclisa may also include trouble sleeping, back pain, peripheral neuropathy, muscle or bone pain, cataract, constipation, rash, COVID-19, and swelling of the hands, legs, ankles and feet.
Heart failure has occurred during treatment with Sarclisa as part of the Isa-Kd combination therapy.
Access and support resources
To explore the access and support resources for Sarclisa that may be available for eligible patients, please visit sarclisa.com/paying-for-sarclisa to enroll in CareASSIST Patient Support by Sanofi. You will be paired with a Case Manager trained to assist you across a spectrum of nonclinical support and personalized guidance.
In closing
This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF intends only to provide you with information that will guide you in discussions with your healthcare team.
To help ensure a good quality of life through effective treatment of your myeloma, you must play an active role in your own medical care. We encourage you to visit myeloma.org for more information and to join the Myeloma Knowledge Platform at myprofile.myeloma.org.
To receive the most up-to-date information about myeloma in a caring and compassionate manner, call the IMF InfoLine at 1.818.487.7455, email InfoLine@myeloma.org, or schedule a time to talk with an IMF InfoLine Coordinator at mmsm.link/infoline.
To get answers to your questions without having to wait, ask Myelo® anytime 24/7 at myeloma.org. This generative AI assistant is designed to help you find the right resources.
Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF. Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.
The International Myeloma Foundation (IMF) is the global leader in myeloma. Our mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® (BSRI®) is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. We also fund innovative research through the IMF Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of videos and free publications in multiple languages to inform and empower patients and care partners to navigate their myeloma journey. All IMF seminars, webinars, and workshops are free-of-charge and designed to directly connect the patient community with expert myeloma clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for the management of myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT Studies show that social support can greatly improve the quality of life of people with cancer. The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering myeloma, care partners of patients with myeloma, and patients who do not have care partners. The IMF InfoLine answers myeloma-related questions. Myelo®, the IMF’s generative AI assistant, is available 24/7 to help you find the right resources.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.