- Phase 3 data showed Sarclisa added to carfilzomib, lenalidomide and dexamethasone (KRd) in patients with newly diagnosed, transplant-eligible multiple myeloma resulted in 77% of patients achieving minimal residual disease (MRD) negativity after consolidation therapy, detected with a sensitivity of 10-5
- MRD negativity rate measured at a sensitivity of 10-6 was 67% for Sarclisa combination therapy
- Results shared during oral presentation at ASH 2023 plenary scientific session
PARIS, December 11, 2023. The Phase 3 trial investigating Sarclisa® (isatuximab-irfc) in combination with carfilzomib, lenalidomide and dexamethasone (KRd) showed a statistically significant improvement in the rate of minimal residual disease (MRD) negativity, compared with KRd alone, after autologous stem cell transplant (ASCT) consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (MM). These results from the IsKia trial conducted by the European Myeloma Network (EMN) were presented during the oral plenary session (#4) at the American Society of Hematology (ASH) Annual Meeting by Francesca Gay, Associate Professor at the University Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino and Department of Molecular Biotechnology and Health Sciences - member of the Young EMN board of directors.
MRD negativity is defined as the absence of myeloma cells in the bone marrow after treatment, as measured by diagnostic techniques that must have a sensitivity of at least 1 in 100,000 cells. In this trial, MRD negativity was detected with a sensitivity of 10-5 (no cancer cells detected within 100,000 bone marrow cells) and 10-6 (no cancer cells detected within 1,000,000 bone marrow cells).
In an intent-to-treat (ITT) analysis, the primary endpoint of rate of MRD negativity using next generation sequencing with a sensitivity of 10-5 after consolidation for patients receiving Sarclisa combination therapy (n=151) was 77% versus 67% for those who received KRd alone (n=151) (odds ratio [OR] 1.67; p=0.049). The respective rates of MRD negativity at sensitivity of 10-6 were 67% versus 48% (OR 1.93; p=0.006). The MRD negativity benefit, both at 10-5 and 10-6 sensitivities, was retained in all subgroups analyzed with similar benefit in both standard-risk and high-risk patients.
There was a statistically significant difference in MRD negativity rates after induction with Sarclisa in combination with KRd versus KRd (10-5: 45% versus 26%, p<0.001; 10-6: 27% versus 14%, p=0.004).
The safety and tolerability of Sarclisa observed in this trial were consistent with the observed safety profile of Sarclisa in other clinical trials, with no new safety signals observed. Rates of grade 3 or higher hematologic adverse events (AEs) were 40% versus 30% and rates of non-hematologic AEs were 41% versus 37% for the Sarclisa combination versus KRd, respectively. Discontinuation rates for AEs were similar in both study arms (7% and 5%, respectively). There were three treatment-related deaths in the Sarclisa combination arm and one in the KRd arm.
Peter C. Adamson
Global Development Head, Oncology
“The statistically significant rates of MRD negativity observed with Sarclisa combination therapy further support our belief in Sarclisa as a potential best-in-class therapy. Effective front-line treatment is critical for newly diagnosed patients, because achieving undetectable levels of disease early in the treatment journey may lead to better long-term outcomes. We look forward to our continued collaboration with the EMN to explore the potential of this novel combination regimen for those with transplant-eligible, newly diagnosed multiple myeloma.”
The use of Sarclisa in combination with KRd in this patient population is investigational and has not been evaluated by any regulatory authority.
About the trial
The randomized, open-label Phase 3 IsKia trial enrolled 302 patients with newly diagnosed, transplant-eligible MM across eight countries and 42 sites in Europe. Patients were randomized into two arms. Patients in both arms received induction with four 28-day cycles of KRd followed by cyclophosphamide and stem cell collections, chemotherapy with Melphalan 200 mg/m2 followed by ASCT (Mel200-ASCT), four 28-day cycles of KRd post ASCT consolidation and 12 cycles of KRd light consolidation. Sarclisa was added to KRd in one trial arm only. During the trial, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for the first four weeks of cycle one, then every other week for the rest of the induction and full consolidation periods, then every four weeks during light consolidation period.
The primary endpoint was the rate of MRD negativity by next-generation sequencing (10-5) after consolidation in the ITT population. MRD was tested in all patients who achieved at least a very good partial response. Key secondary endpoints were the rate of next-generation sequencing MRD negativity (10-5) after induction and progression free survival. MRD rates were evaluated in an ITT analysis.
High-risk patient cytogenetics per the International Myeloma Working Group (IMWG) criteria were defined as the presence of t(4;14), t(14;16), or del(17p). High-risk cytogenetic abnormality (HRCA) was defined as the presence of one of the following abnormalities: del(17p13.1), t(4;14) (p16.3;q32.3), t(14;16) (q32.3;q23), gain(1q21), or amp(1q21). Two or more HRCAs was defined as the presence of at least two high-risk cytogenetic abnormalities.
About Sarclisa
Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activities. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.
Based on the Phase 3 ICARIA-MM study, Sarclisa is approved in >50 countries, including the U.S. and EU, in combination with pomalidomide and dexamethasone for the treatment of certain patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the Phase 3 IKEMA study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the U.S. for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the U.S., the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).
The IsKia trial marks the second positive Phase 3 trial of Sarclisa in transplant-eligible newly diagnosed multiple myeloma, and fifth positive Phase 3 readout for Sarclisa overall, demonstrating its best-in-class potential.
Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.
For more information on Sarclisa clinical trials, please visit www.clinicaltrials.gov.
About multiple myeloma
MM is the second most common hematologic malignancy.i Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.
About the European Myeloma Network (EMN) foundation
The European Myeloma Network (EMN) is a non-profit organization, created in 2005. This network is the reference organization for multiple myeloma studies in Europe: physicians can participate in cooperative projects to increase and share their experiences, and to standardize and harmonize clinical practices; pharmaceutical companies can refer to the EMN as a general interlocutor in Europe to plan and manage clinical trials with new molecules; and, most importantly, patients can be enrolled in clinical studies evaluating last-generation and promising drugs, with the ultimate goal of improving their survival and quality of life. Various national groups collaborate within the EMN, such as the Netherlands (where the headquarter is located), Italy (with the data centre of the network), Germany, Austria, France, Spain, Greece, Czech Republic, the UK, Norway, Denmark, Switzerland, Turkey, and many more countries will participate in the EMN projects in the future. For further information, please contact the EMN (President Prof. Pieter Sonneveld): https://www.myeloma-europe.org/
IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS
What is SARCLISA?
SARCLISA is a prescription medicine used in combination with:
- The medicines pomalidomide and dexamethasone, to treat adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor to treat multiple myeloma.
- The medicines carfilzomib and dexamethasone, to treat adults with multiple myeloma who have already received 1 to 3 lines of treatment and they did not work or are no longer working.
It is not known if SARCLISA is safe and effective in children.
Important Safety Information
Do not receive SARCLISA if you have a history of a severe allergic reaction to isatuximab-irfc or any of the ingredients in SARCLISA (see the list of ingredients in the full Prescribing Information).
Before receiving SARCLISA, tell your healthcare provider about all of your medical conditions, including if you:
- Have heart problems, if your healthcare provider prescribes SARCLISA in combination with carfilzomib and dexamethasone for you.
- Have had shingles (herpes zoster).
- Are pregnant or plan to become pregnant. SARCLISA may harm your unborn baby.
- Females who are able to become pregnant should use an effective method of birth control during treatment and for 5 months after your last dose of SARCLISA. Talk to your healthcare provider about birth control methods that you can use during this time.
- Tell your healthcare provider right away if you think you are pregnant or become pregnant during treatment with SARCLISA.
- Before receiving SARCLISA in combination with pomalidomide, females and males must agree to the instructions in the pomalidomide REMS program. The pomalidomide REMS program has specific requirements about birth control, pregnancy testing, blood donation, and sperm donation that you need to know. Talk to your healthcare provider to learn more about pomalidomide.
- Are breastfeeding or plan to breastfeed. It is not known if SARCLISA passes into your breast milk. You should not breastfeed during treatment with SARCLISA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How will I receive SARCLISA?
- SARCLISA will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.
- SARCLISA is given in treatment cycles of 28 days (4 weeks), together with either the medicines pomalidomide and dexamethasone, or carfilzomib and dexamethasone.
- In cycle 1, SARCLISA is usually given weekly.
- Starting in cycle 2, SARCLISA is usually given every 2 weeks.
- If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.
- Your healthcare provider will give you medicines before each dose of SARCLISA to help reduce the risk of infusion reactions (make them less frequent and severe).
What are the possible side effects of SARCLISA?
SARCLISA may cause serious side effects, including:
- Infusion reactions. Infusion reactions are common with SARCLISA and can sometimes be severe or life threatening.
- Your healthcare provider will prescribe medicines before each infusion of SARCLISA to help decrease your risk for infusion reactions or to help make any infusion reaction less severe. You will be monitored for infusion reactions during each dose of SARCLISA.
- Your healthcare provider may slow down or stop your infusion, or completely stop treatment with SARCLISA if you have an infusion reaction.
Get medical help right away if you develop any of the following symptoms of infusion reaction during or after an infusion of SARCLISA:
- shortness of breath, wheezing, or trouble breathing
- swelling of the face, mouth, throat, or tongue
- throat tightness
- palpitations
- dizziness, lightheadedness, or fainting
- headache
- cough
- rash or itching
- nausea
- runny or stuffy nose
- chills
- Decreased white blood cell counts. Decreased white blood cell counts are common with SARCLISA and certain white blood cells can be severely decreased. You may have an increased risk of getting certain infections, such as upper and lower respiratory tract infections and urinary tract infections.
- Your healthcare provider will check your blood cell counts during treatment with SARCLISA. Your healthcare provider may prescribe an antibiotic or antiviral medicine to help prevent infection, or a medicine to help increase your white blood cell counts during treatment with SARCLISA.
Tell your healthcare provider right away if you develop any fever or symptoms of infection during treatment with SARCLISA.
- Risk of new cancers. New cancers have happened in people during treatment with SARCLISA. Your healthcare provider will monitor you for new cancers during treatment with SARCLISA.
- Change in blood tests. SARCLISA can affect the results of blood tests to match your blood type. Your healthcare provider will do blood tests to match your blood type before you start treatment with SARCLISA. Tell all of your healthcare providers that you are being treated with SARCLISA before receiving blood transfusions.
The most common side effects of SARCLISA in combination with pomalidomide and dexamethasone include:
- upper respiratory tract infection
- lung infection (pneumonia)
- diarrhea
- decreased red blood cell count (anemia)
- decreased platelet count (thrombocytopenia)
The most common side effects of SARCLISA in combination with carfilzomib and dexamethasone include:
- upper respiratory tract infection
- tiredness and weakness
- high blood pressure
- diarrhea
- lung infection (pneumonia)
- trouble breathing
- trouble sleeping
- bronchitis
- cough
- back pain
- decreased red blood cell count (anemia)
- decreased platelet count (thrombocytopenia)
Heart failure can happen during treatment with SARCLISA in combination with carfilzomib and dexamethasone. Tell your healthcare provider right away if you develop any of the following symptoms:
- trouble breathing
- cough
- swelling of your ankles, feet, or legs
These are not all the possible side effects of SARCLISA. For more information, ask your healthcare provider or pharmacist.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please see full Prescribing Information, including Patient Information
About Sanofi
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i Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676-681. doi:10.1053/j/seminoncol.2016.11.004.