SARCLISA: CLINICAL EVIDENCE
Knowledge of how a treatment impacts the underlying condition is important when evaluating the clinical value that it brings
Mechanism of action: SARCLISA is a multimodal anti-CD38 mAb1
Targeted binding to a specific epitope induces distinct antitumor activity2
Clinical trials for SARCLISA
Newly diagnosed multiple myeloma (NDMM)
SARCLISA + VRd WAS EVALUATED IN IMROZ, A LARGE PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY1
Treatment was administered until disease progression, unacceptable toxicity, or other discontinuation criteria.3
aThe interim analysis of PFS was performed after 162 events of disease progression or death had occurred (73% of the planned 222 events for the final analysis).
bDuring induction, patients in the SARCLISA + VRd group received IV SARCLISA (10 mg/kg of body weight once weekly in Cycle 1, with subsequent cycles occurring every 2 weeks). During continuous treatment, patients received IV SARCLISA (10 mg/kg every 2 weeks, with monthly administration starting with Cycle 18).1
cDuring induction, all patients received VRd, consisting of subcutaneous bortezomib (1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32), oral lenalidomide (25 mg per day on days 1 to 14, and 22 to 35), and oral or IV dexamethasone (20 mg per day on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 22, 23, 25, 26, 29, 30, 32, and 33). During continuous treatment, all patients received an Rd regimen that consisted of oral lenalidomide (25 mg per day on days 1 to 21) and dexamethasone (20 mg per day once weekly).1
dIn the continuous phase, patients randomized to the VRd arm who experienced progressive disease during the Rd treatment period could cross over to receive SARCLISA + Rd.
ePFS results were assessed by an independent review committee based on central laboratory data for M-protein and central radiologic imaging review using the IMWG criteria.
IMWG, International Myeloma Working Group; IV, intravenous; M-protein, monoclonal protein; Rd, lenalidomide and dexamethasone; R-ISS, Revised International Staging System.
PATIENTS WITH POOR PROGNOSTIC FACTORS WERE INCLUDED IN THE PHASE 3 IMROZ TRIAL AND BALANCED ACROSS TREATMENT ARMS3
aThe R-ISS stage at baseline was determined by means of interactive response technology for stratification. The stage was derived from the International Staging System (ISS) stage at enrollment, cytogenetic abnormality (yes vs no), and serum lactate dehydrogenase concentration.
bHigh cytogenetic risk was defined as the presence of del(17p), t(4;14), t(14;16), or a combination of these.
cAbnormality was defined as present in at least 30% of abnormal bone marrow plasma cells for t(4;14), t(14;16), and 1q21+ (at least 3 copies) and at least 50% of abnormal bone marrow plasma cells for del(17p). One patient in the SARCLISA + VRd group had 2 high-risk chromosomal abnormalities (del[17p] and t[4;14]).
eGFR, estimated glomerular filtration rate; HRCA, high-risk chromosomal abnormality; R-ISS, Revised International Staging System; VRd, bortezomib, lenalidomide, and dexamethasone.
With SARCLISA + VRd, patients achieved superior rates of ≥CR1
More than half of patients with ≥CR achieved MRD- with SARCLISA + VRd1
Deep and durable responses to extend frontline remissions for patients1,3
Sustained MRD- status in patients treated with SARCLISA + VRd
Estimated overall survival in patients treated with SARCLISA + VRd
Median time to next treatment (TTNT) in patients treated with SARCLISA + VRd
PFS with SARCLISA + VRd in certain groups with poor prognostic factors3
Adverse reactions with SARCLISA + VRd
ADVERSE REACTIONS (≥20%) IN PATIENTS RECEIVING SARCLISA + VRd1,3
SARCLISA + VRd demonstrated lower rates of peripheral neuropathy than VRd alone: 54% vs 61% (all grades), and comparable rates of Grade ≥3 peripheral neuropathy vs VRd alone (7% vs 6%).
The IMROZ trial was conducted from December 2017 to September 26, 2023 (date of the interim analysis), during the COVID-19 pandemic.
aIncludes other related terms.
bIncludes 1 patient (0.6%) with fatal upper respiratory tract infection.
cPneumonia includes atypical pneumonia, bronchopulmonary aspergillosis, COVID-19 pneumonia, lower respiratory tract infection, Pneumocystis jirovecii pneumonia, pneumonia, pneumonia aspiration, pneumonia bacterial, pneumonia influenzal, pneumonia klebsiella, pneumonia legionella, pneumonia parainfluenzae viral, pneumonia pneumococcal, pneumonia pseudomonal, pneumonia respiratory syncytial viral, pneumonia viral, pulmonary sepsis.
dIncludes 14 patients (5%) with fatal pneumonia.
eIncludes 4 patients (2.2%) with fatal pneumonia.
fCOVID-19 includes COVID-19 infections other than COVID-19 pneumonia.
gIncludes 2 patients (1.1%) with fatal COVID-19.
hFatigue includes fatigue, asthenia, or malaise.
iRash includes dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis exfoliative generalized, drug eruption, rash, rash erythematous, rash macular, rash maculopapular, rash pruritic, rash pustular, skin exfoliation, skin hyperpigmentation, skin lesion, skin reaction, and toxic skin eruption.
COVID-19, coronavirus disease 19; IRR, infusion-related reaction; VRd, bortezomib, lenalidomide, and dexamethasone.
Additional safety data for SARCLISA + VRd1,3
Serious adverse events
- Serious adverse reactions occurred in 71% of patients receiving SARCLISA + VRd
- The serious adverse reaction in >5% of patients who received SARCLISA + VRd was pneumonia (30%)
- Fatal adverse reactions (Grade 5 treatment-emergent adverse events) were reported in 11% of patients with SARCLISA + VRd (those occurring in more than 1% of patients were pneumonia [5%]) vs 5.5% of patients with VRd alone
HEMATOLOGY LABORATORY IN PATIENTS RECEIVING SARCLISA + VRd VS VRd ALONE
The denominator used to calculate the rate is based on the number of patients with a baseline value and at least one post-baseline value.
- Patients should be monitored for signs and symptoms of infection prior to and during treatment with SARCLISA and treated appropriately. Prophylactic antimicrobials should be administered according to guidelines
- Permanent discontinuations due to adverse events were similar across arms: 23% for SARCLISA + VRd and 26% for VRd alone
Infusion-related reactions (IRRs)
- Across 3 clinical trials, IRRs occurred in 35% of patients receiving SARCLISA (n=206/592). Among these patients, 92% experienced IRRs during the first infusion and 12% after the first cycle
- Grade 1 IRRs were reported in 6% of patients receiving SARCLISA, Grade 2 in 28%, and Grade 3 or 4 in 1.2% across the 3 clinical trials
- IRRs may require interruption, management, and/or discontinuation of the infusion
Second primary malignancies
- Monitor patients for the development of second primary malignancies
- In the IMROZ trial, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients in the SARCLISA + VRd arm and in 9% of patients in the VRd arm
Median treatment duration
- Median treatment duration was 53 months for SARCLISA + VRd (n=263) vs 31 months with VRd alone (n=181)
Relapsed or refractory multiple myeloma (RRMM)
Patients who have received 1 to 3 prior lines of therapy in combination with carfilzomib and dexamethasone (Kd)
IKEMA study
SARCLISA + Kd WAS EVALUATED IN THE IKEMA PHASE 3, MULTICENTER, MULTINATIONAL, RANDOMIZED, OPEN-LABEL STUDY1,8
Treatment was administered in both groups in 28-day cycles until disease progression or unacceptable toxicity.1
aPatients were excluded if they were refractory to prior anti-CD38 therapy or had received prior carfilzomib treatment.8
bSARCLISA 10 mg/kg was administered as an IV infusion weekly in the first cycle and every 2 weeks thereafter.8
cCarfilzomib was administered as an IV infusion at the dose of 20 mg/m2 on days 1 and 2, 56 mg/m2 on days 8, 9, 15, and 16 of cycle 1, and at the dose of 56 mg/m2 on days 1, 2, 8, 9, 15, and 16 for subsequent cycles of each 28-day cycle. Dexamethasone (IV on the days of SARCLISA and/or carfilzomib infusions and orally on the other days) 20 mg was given on days 1, 2, 8, 9, 15, 16, 22, and 23 for each 28-day cycle.8
dPFS results were assessed by an IRC, based on central laboratory data for M-protein, and central radiologic imaging review using the International Myeloma Working Group (IMWG) criteria. An interim analysis was conducted when 65% of the 159 PFS events (ie, 103 events) were observed.8
IMWG, International Myeloma Working Group; IRC, independent review committee; IV, intravenous; M-protein, monoclonal protein.
IKEMA primary endpoint
Interim analysis
SARCLISA + carfilzomib and dexamethasone (Kd) demonstrated superior PFS vs Kd alone. Median PFS (mPFS) with SARCLISA + Kd was not yet reached (NR), with a hazard ratio (HR) of 0.548 (95% CI: 0.37, 0.82; P=0.0032)* vs Kd alone at a median follow-up of 20.7 months. The median duration of treatment in the SARCLISA + Kd group was 80 weeks vs 61 weeks for the Kd group.1
Reduction in risk of progression or death1
Final analysis
A prespecified final analysis was conducted when 159 PFS events were observed, with a median follow-up of 44 months.9 This is the longest ever reported in a phase 3 trial that included lenalidomide-refractory patients.4,10-13†
*Stratified by the number of previous lines of therapy (1 vs >1) and Revised International Staging System stage (I or II vs III vs not classified) according to interactive response technology.
†Based on a review of published phase 3 trials that included lenalidomide-refractory patients with RRMM. Interpret with caution, as various factors, including patient population, differ between trials.
IKEMA secondary endpoints
A majority of patients treated with SARCLISA achieved VGPR or better.8,9
RESPONSE RATES ACROSS TREATMENT ARMS
| FINAL ANALYSIS: 44 MONTHS MEDIAN FOLLOW-UP9 | INTERIM ANALYSIS: 21 MONTHS MEDIAN FOLLOW-UP8 | |||
| Secondary outcomesa | SARCLISA + Kd (n=179) | Kd (n=123) | SARCLISA + Kd (n=179) | Kd (n=123) |
| ORR | 87% | 84% | 87% | 83% |
| ≥VGPR | 73% | 56% | 73% | 56% |
| CR | 44% | 29% | 40% | 28% |
| MRD- (ITT) | 34% | 15% | 30% | 13% |
As ORR did not reach statistical significance, CR and VGPR were not tested for significance.
Study limitations: As ORR did not reach statistical significance, ≥VGPR, minimal residual disease negativity (MRD-), and CR were not tested for significance. According to the US Food and Drug Administration (FDA), using MRD to assess clinical benefit of an MM treatment should only be assessed in patients who achieve a CR or stringent CR. In the IKEMA trial, MRD was assessed in patients who achieved ≥VGPR. Additionally, there was an amount of missing data that did not meet the FDA’s threshold for label inclusion. This analysis requires cautious interpretation, and clinical significance of these data is unknown.
aStringent CR, CR, VGPR, and partial response (PR) were evaluated by the IRC using the IMWG response criteria. Final analysis results were based on a prespecified final analysis with a median follow-up time of 43.96 months. Interim analysis results were based on prespecified interim analysis with a median follow-up time of 20.7 months.
CR, complete response; ITT, intent to treat; Kd, carfilzomib and dexamethasone; MRD-, minimal residual disease negative/negativity; ORR, overall response rate; VGPR, very good partial response.
SUBGROUP ANALYSIS9
50%
reduction in risk of progression or death in patients aged ≥65 years
HR=0.497
(95% CI: 0.321, 0.771)
42%
reduction in risk of disease progression in patients with gain (1q21)
HR=0.582
(95% CI: 0.368, 0.923)
28%
reduction in risk of disease progression in patients with high-risk
cytogenetic status
HR=0.724
(95% CI: 0.406, 1.290)
41%
reduction in risk of progression or death in lenalidomide-refractory patients
HR=0.586
(95% CI: 0.353, 0.972)
39%
reduction in risk of progression or
death in International Staging
System (ISS) stage III patients
HR=0.607
(95% CI: 0.290, 1.268)
44%
reduction in risk of progression or
death in renally impaired patients
HR=0.562
(95% CI: 0.266, 1.189)
Study limitations: Definitive conclusions cannot be made as this analysis was not statistically powered in this trial. All subgroups were prespecified except the lenalidomide-refractory subgroup. Subgroups were not powered to show differences between treatment arms.
Final analysis: 44 months median follow-up
IKEMA safety
Interim analysis: 21 months median follow-up
ADVERSE REACTIONS (≥10%) IN PATIENTS RECEIVING SARCLISA + Kd WITH A DIFFERENCE BETWEEN ARMS OF ≥5% COMPARED WITH Kd ALONE1
| ADVERSE REACTION | SARCLISA + Kd (n=177) | Kd (n=122) | ||||
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| General disorders and administration site conditions | ||||||
| Infusion-related reactiona | 46% | 0.6% | 0% | 3.3% | 0% | 0% |
| Fatigueb | 42% | 5% | 0% | 32% | 3.3% | 0% |
| Infections | ||||||
| Upper respiratory tract infectionc | 67% | 9% | 0% | 57% | 7% | 0% |
| Pneumoniad | 36% | 19% | 3.4% | 30% | 15% | 2.5% |
| Bronchitise | 24% | 2.3% | 0% | 13% | 0.8% | 0% |
| Vascular disorders | ||||||
| Hypertensionf | 37% | 20% | 0.6% | 0.6% | 0.6% | 0.6% |
| Respiratory, thoracic, and mediastinal disorders | ||||||
| Dyspneag | 29% | 5% | 0% | 24% | 0.8% | 0.8% |
| Coughh | 23% | 0% | 0% | 15% | 0% | 0% |
| Gastrointestinal disorders | ||||||
| Diarrhea | 36% | 2.8% | 0% | 29% | 2.5% | 0% |
| Vomiting | 15% | 1.1% | 0% | 9% | 0.8% | 0% |
aInfusion-related reaction includes infusion-related reaction, cytokine release syndrome, and hypersensitivity.
bFatigue includes fatigue and asthenia.
cUpper respiratory tract infection includes acute sinusitis, chronic sinusitis, H1N1 influenza, H3N2 influenza, influenza, laryngitis, laryngitis viral, nasal herpes, nasopharyngitis, pharyngitis, pharyngotonsillitis, respiratory syncytial virus infection, rhinitis, sinusitis, sinusitis bacterial, tonsillitis, tracheitis, upper respiratory tract infection, viral rhinitis, respiratory tract infection, respiratory tract infection viral, influenza-like illness, parainfluenza virus infection, respiratory tract infection bacterial, and viral upper respiratory tract infection.
dPneumonia includes atypical pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, Pneumocystis jirovecii pneumonia, pneumonia, pneumonia influenzal, pneumonia legionella, pneumonia pneumococcal, pneumonia respiratory syncytial viral, pneumonia streptococcal, pneumonia viral, pulmonary sepsis, and pulmonary tuberculosis.
eBronchitis includes bronchitis, bronchitis viral, respiratory syncytial virus bronchitis, bronchitis chronic, and tracheobronchitis.
fHypertension includes hypertension, blood pressure increased, and hypertensive crisis.
gDyspnea includes dyspnea and dyspnea exertional.
hCough includes cough, productive cough, and allergic cough.
Kd, carfilzomib and dexamethasone.
Serious adverse reactions
Serious adverse reactions occurred in 59% of patients receiving SARCLISA + Kd. The most frequent serious adverse reactions in >5% of patients who received SARCLISA + Kd were pneumonia (25%) and upper respiratory tract infections (9%)1
Fatal adverse reactions occurred in 3.4% of patients receiving SARCLISA + Kd (those occurring in >1% of patients were pneumonia in 1.7% and cardiac failure in 1.1% of patients) vs 3.3% in the Kd arm1,8
HEMATOLOGY LABORATORY ABNORMALITIES IN PATIENTS RECEIVING SARCLISA + Kd VS Kd ALONE1
| LABARATORY PARAMETER | SARCLISA + Kd (n=177) | Kd (n=122) | ||||
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| Hemoglobin decreased | 99% | 22% | 0% | 99% | 20% | 0% |
| Lymphocytes decreased | 94% | 52% | 17% | 95% | 43% | 14% |
| Platelets decreased | 94% | 19% | 11% | 88% | 16% | 8% |
| Neutrophils decreased | 55% | 18% | 1.7% | 43% | 7% | 0.8% |
The denominator used to calculate the percentage was based on safety population.
Kd, carfilzomib and dexamethasone.
Complete blood cell counts should be monitored periodically during treatment. Patients with neutropenia should be monitored for signs of infection. In case of infection, appropriate standard therapy should be instituted. Antibacterial and antiviral prophylaxis can be considered during treatment.1
Cardiac failure
Cardiac failure (including cardiac failure, cardiac failure congestive, cardiac failure acute, cardiac failure chronic, left ventricular failure, and pulmonary edema) was reported in 7% of patients receiving SARCLISA + Kd (Grade ≥3 in 4%) and in 7% of patients receiving Kd (Grade ≥3 in 4.1%)1
Serious cardiac failure was observed in 4% of patients receiving SARCLISA + Kd and in 3.3% of patients receiving Kd1
Permanent treatment discontinuation due to adverse reactions (Grades 1-4)
8% of patients receiving SARCLISA + Kd discontinued treatment due to adverse reactions vs 14% of patients receiving Kd alone1,8
The most frequent adverse reactions requiring permanent discontinuation were infections (2.8%, SARCLISA + Kd; 4.9%, Kd)1
Dosage interruptions due to an adverse reaction occurred in 33% of patients who received SARCLISA. The most frequent adverse reaction requiring dosage interruption was infusion-related reaction (30%)1
Infusion-related reactions (IRRs)1
- IRRs were reported in 81 patients (46%) treated with SARCLISA + Kd
- Grade 1 IRRs were reported in 14%, Grade 2 in 32%, and Grade 3 in 0.6% of the patients treated with SARCLISA + Kd
- Signs and symptoms of Grade 3 IRRs included dyspnea and hypertension
- SARCLISA was discontinued in 0.6% of patients due to IRRs
Final analysis: 44 months median follow-up
OVERVIEW OF TEAEs AND TREATMENT DISCONTINUATIONS8,18
| SARCLISA + Kd (n=177) | Kd (n=122) | |||||
| Median treatment exposure | 94 weeks | 62 weeks | ||||
| Serious adverse reactions | 70.1% | 59.8% | ||||
| Fatal adverse reactions | 5.6% | 4.9% | ||||
| Cardiac failure, Grade ≥ 3 (any classa) | 4.5% | 4.1% | ||||
| Permanent discontinuation due to adverse reactions (Grades 1-4) | 12.4% | 18% | ||||
aGrouping using MedDRA SMQ cardiac failure narrow terms.
Kd, carfilzomib and dexamethasone; MedDRA, Medical Dictionary for Regulatory Activities; SMQ, Standardised MedDRA Queries; TEAE, treatment-emergent adverse event.
The safety profile at the longer follow-up remained consistent with the interim analysis, with the most frequent adverse reactions being IRRs (45.8%), diarrhea (39.5%), hypertension (37.9%), and upper respiratory tract infections (37.3%).9
Patients who have received at least 2 prior therapies (including lenalidomide and a proteasome inhibitor) in combination with pomalidomide and dexamethasone (Pd)
ICARIA study
THE RANDOMIZED, MULTICENTER, OBSERVATIONAL ICARIA TRIAL WAS THE FIRST PHASE 3 TRIAL EVALUATING A CD38-DIRECTED MONOCLONAL ANTIBODY + Pd VS Pd ALONE IN ADULTS WITH RRMM1
aThe median duration of treatment was 41 weeks for SARCLISA + Pd arm compared with 24 weeks for Pd arm. Treatment administered in 28-day cycles until disease progression or unacceptable toxicity.
bOf each 28-day cycle.
IV, intravenous; PI, proteasome inhibitor; Pd, pomalidomide and dexamethasone; RRMM, relapsed or refractory multiple myeloma.
ICARIA primary endpoint
ICARIA secondary endpoint
ICARIA safety
ADVERSE REACTIONS (≥10%) IN PATIENTS RECEIVING SARCLISA + Pd WITH A DIFFERENCE BETWEEN ARMS OF ≥5% COMPARED WITH CONTROL ARM1
| ADVERSE REACTION | SARCLISA + Kd (n=152) | Kd (n=149) | ||||
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| IRRs | 38% | 1.3% | 1.3% | 0% | 0% | 0% |
| Infections | ||||||
| Upper respiratory tract infectiona | 57% | 9% | 0% | 42% | 3.4% | 0% |
| Pneumoniab | 31% | 22% | 3.3% | 23% | 16% | 2.7% |
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 12% | 11% | 1.3% | 2% | 1.3% | 0.7% |
| Respiratory, thoracic, and mediastinal disorders | ||||||
| Dyspneac | 12% | 11% | 1.3% | 12% | 1.3% | 0% |
| Gastrointestinal disorders | ||||||
| Diarrhea | 26% | 5% | 0% | 19% | 0.7% | 0% |
| Nausea | 15% | 0% | 0% | 9% | 0% | 0% |
| Vomiting | 12% | 1.3% | 0% | 3.4% | 0% | 0% |
aUpper respiratory tract infection includes bronchiolitis, bronchitis, bronchitis viral, chronic sinusitis, fungal pharyngitis, influenza-like illness, laryngitis, nasopharyngitis, parainfluenza virus infection, pharyngitis, respiratory tract infection, respiratory tract infection viral, rhinitis, sinusitis, tracheitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.
bPneumonia includes atypical pneumonia, bronchopulmonary aspergillosis, pneumonia, pneumonia haemophilus, pneumonia influenzal, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, candida pneumonia, pneumonia bacterial, haemophilus infection, lung infection, pneumonia fungal, and Pneumocystis jirovecii pneumonia.
cDyspnea includes dyspnea, dyspnea exertional, and dyspnea at rest.
IRR, infusion-related reaction; Pd, pomalidomide and dexamethasone.
HEMATOLOGY LABORATORY ABNORMALITIES IN PATIENTS RECEIVING SARCLISA + Pd VS Pd ALONE1
| LABARATORY PARAMETER | SARCLISA + Pd (n=152) | Pd (n=149) | ||||
| All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 | |
| Hemoglobin decreased | 99% | 32% | 0% | 97% | 28% | 0% |
| Neutrophils | 96% | 24% | 61% | 92% | 38% | 31% |
| Lymphocytes | 92% | 42% | 13% | 92% | 35% | 8% |
| Platelets | 84% | 14% | 16% | 79% | 9% | 15% |
The denominator used to calculate the percentages was based on the safety population.
Pd, pomalidomide and dexamethasone.
Complete blood cell counts should be monitored periodically during treatment. Patients with neutropenia should be monitored for signs of infection. In case of infection, appropriate standard therapy should be instituted. Antibacterial and antiviral prophylaxis can be considered during treatment.1
Infusion-related reactions (IRRs)1
IRRs were reported in 58 patients (38%) treated with SARCLISA. All patients who experienced IRRs experienced them during the first infusion of SARCLISA, with 3 patients (2%) also having IRRs at their second infusion, and 2 patients (1.3%) at their fourth infusion
Grade 1 IRRs were reported in 3.9%, Grade 2 in 32%, Grade 3 in 1.3%, and Grade 4 in 1.3% of the patients
Signs and symptoms of Grade 3 or 4 IRRs included dyspnea, hypertension, and bronchospasm
The incidence of infusion interruptions because of IRRs was 30%. The median time to infusion interruption was 55 minutes
SARCLISA was discontinued in 2.6% of patients due to IRRs
IRRs are defined as adverse reactions associated with the SARCLISA infusion, with an onset typically within 24 hours from the start of the infusion.
Serious and fatal adverse reactions1
Serious adverse reactions occurred in 62% of patients receiving SARCLISA + Pd
- Serious adverse reactions in >5% of patients who received SARCLISA + Pd included pneumonia (26%), upper respiratory tract infection (7%), and febrile neutropenia (7%)
Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%])
Discontinuation rates1
Dosage interruptions due to an adverse reaction occurred in 31% of patients who received SARCLISA + Pd
- Discontinuations from treatment due to infection were reported in 2.6% of patientsreceiving SARCLISA + Pd vs 5% of patients receiving Pd alone
- The most frequent adverse reaction requiring dosage interruption was IRR (28%)
Dosing and administration1
Premedication
The following premedications should be administered prior to SARCLISA infusion to reduce the risk and sensitivity of infusion-related reactions (IRRs).
|
Dexamethasone | NDMM | RRMM |
| When administered in combination with SARCLISA, bortezomib, and lenalidomide: | When administered in combination with SARCLISA and carfilzomib: When administered in combination with SARCLISA and pomalidomide: | |
| Acetaminophen | 650 mg or 1,000 mg orally (or equivalent) | |
| H2 Antagonists | Institution-preferred agent | |
| Diphenhydramine | 25 mg to 50 mg orally or intravenously (or equivalent). The intravenous route is preferred for at least the first 4 infusions | |
The above recommended dose of dexamethasone (orally or intravenously) corresponds to the total dose to be administered only once before infusion as part of the premedication and of the backbone treatment, before SARCLISA and carfilzomib or SARCLISA and pomalidomide administration. Administer the recommended premedication agents 15 to 60 minutes prior to starting a SARCLISA infusion. No post-infusion medications are required for SARCLISA.
Recommended antimicrobial prophylaxis
Initiate antiviral prophylaxis to prevent herpes zoster reactivation based on standard guidelines.
Recommended dose
10 mg/kg actual body weight administered as an intravenous infusion in combination with VRd, Kd, or Pd
250 mL fixed infusion volume
Treatment is repeated until disease progression or unacceptable toxicity
Kd, carfilzomib and dexamethasone; Pd, pomalidomide and dexamethasone; VRd, bortezomib, lenalidomide, and dexamethasone.
For patients with NDMM not eligible for transplant
SARCLISA dosing schedule in combination with VRd1
The recommended dose of SARCLISA is 10 mg/kg administered as an intravenous infusion at a fixed infusion volume of 250 mL in combination with bortezomib, lenalidomide, and dexamethasone (VRd).
For additional dosing instructions for combination agents administered with SARCLISA, refer to the respective manufacturer’s Prescribing Information.
aInitiates after cycle 17.
bInduction phase cycles=42 days each.
cContinuous phase cycles=28 days each.
RRMM dosing schedule
SARCLISA dosing schedule in combination with Kd or Pd1
The recommended dose of SARCLISA is 10 mg/kg administered as an intravenous infusion at a fixed infusion volume of 250 mL in combination with either Kd or Pd.
On days where both SARCLISA and carfilzomib are administered, administer dexamethasone first, followed by SARCLISA infusion, then followed by carfilzomib infusion.
For additional dosing instructions for combination agents administered with SARCLISA, refer to the respective manufacturer’s Prescribing Information.
Infusion times decrease to 75 minutes after the second infusion in the absence of IRRs
The required dose of SARCLISA (in mg) should be calculated based on actual patient weight (measured prior to each cycle to have the administered dose adjusted accordingly). Note that more than 1 SARCLISA vial may be necessary to obtain the required dose for the patient. Incremental escalation of the infusion rate should be considered only in the absence of IRRs.
INFUSION RATES
| Dilution volume | Initial rate | Absence of IRR | Rate increment | Maximum rate | Total time | |
| First infusion | 250 mL | 25 mL/h | For 60 min | 25 mL/h every 30 min | 150 mL/h | 3 h 20 min |
| Second infusion | 250 mL | 50 mL/h | For 60 min | 50 mL/h for 30 min, then increase by 100 mL/h | 200 mL/h | 1 h 53 min |
| Subsequent infusion | 250 mL | 200 mL/h | - | - | 200 mL/h | 75 m |
SARCLISA should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage IRRs if they occur.
IRR, infusion-related reaction.
The value of SARCLISA
Explore the cost comparison of SARCLISA in the first
5 years of treatment for multiple myeloma.
Connect with us
Schedule a meeting with a member of the Sanofi Market Access team to learn more about Sanofi products.
References: 1. SARCLISA. Prescribing information. sanofi-aventis U.S. LLC; 2023. 2. Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, openlabel, phase 3 study. Lancet. 2019;394(10214):2096-2107. doi:10.1016/S0140-6736(19)32556-5 3. Facon T, Dimopoulos MA, Leleu XP, et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(17):1597-1609. doi:10.1056/NEJMoa2400712 4. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-e346. doi:10.1016/S1470-2045(16)30206-6 5. Facon T, Dimopoulos MA, Leleu X, et al. Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ). Presented at: 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL. 6. Hagiwara M, Panjabi S, Delea T, Yucel E, Fonseca R. Burden of disease progression in patients with multiple myeloma in the US. Leuk Lymphoma. 2020;61(1):47-55. doi:10.1080/10428194.2019.1648802 7. Campbell BA, Scarisbrick JJ, Kim YH, Wilcox RA, McCormack C, Prince HM. Time to next treatment as a meaningful endpoint for trials of primary cutaneous lymphoma. Cancers (Basel). 2020;12(8):2311. doi:10.3390/cancers12082311 8. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4 9. Martin T, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized phase 3 study. Blood Cancer J. 2023;13(1):72. doi:10.1038/s41408-023-00797-8 10. Bisht K, Walker B, Kumar SK, et al. Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies. Expert Rev Hematol. 2021;14(12):1099-1114. doi:10.1080/17474086.2021.1983427 11. Lecat CSY, Taube JB, Wilson W, et al. Defining unmet need following lenalidomide refractoriness: real-world evidence of outcomes in patients with multiple myeloma. Front Oncol. 2021;11:703233. doi:10.3389/fonc.2021.703233 12. Greipp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-3420. doi:10.1200/JCO.2005.04.242 13. Hari P, Romanus D, Luptakova K, et al. The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies. J Geriatr Oncol. 2018;9(2):138-144. doi:10.1016/j.jgo.2017.09.007 14. Data on file; IKEMA CSR. sanofi-aventis U.S. LLC. 15. Hernández-Rivas JA, Ríos-Tamayo R, Encinas C, Alonso R, Lahuerta JJ. The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies. Biomark Res. 2022;10(1):1-23. doi:10.1186/s40364-021-00344-2 16. Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23(1):65-76. doi:10.1016/S1470-2045(21)00579-9 17. Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007;25(25):3892-3901. doi:10.1200/JCO.2006.10.5460 18. Martin T, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized phase 3 study. Blood Cancer J. 2023;13(1) (suppl):1-12. doi:10.1038/s41408-023-00797-8 19. Moreau P, Dimopoulos MA, Mikhael J, et al; IKEMA study group. Updated progression-free survival and depth of response in IKEMA, a randomized phase 3 trial of isatuximab, carfilzomib and dexamethasone (Isa-Kd) vs Kd in relapsed multiple myeloma. Presented at: The 8th World Congress on Controversies in Multiple Myeloma (COMy); May 12-15, 2022; Paris, France. 20. Data on file; ICARIA CSR. sanofi-aventis U.S. LLC.
INDICATION
SARCLISA (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated:
-
In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
-
In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy
-
In combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Serious infusion-related reactions (IRRs), including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle.
The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone.
Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) IRR occurs and institute appropriate management.
Infections
SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia (32%).
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
SARCLISA may cause neutropenia.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%.
Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%).
In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) and in 2% of patients treated with Pd.
In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients treated with SARCLISA, carfilzomib, and dexamethasone (Isa-Kd) and in 8% of patients treated with Kd.
In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) and in 9% of patients treated with VRd.
The most common (≥1%) second primary malignancies in ICARIA-MM, IKEMA, and IMROZ (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer, except 2 patients in the Isa-VRd arm and 1 patient in the VRd arm of the IMROZ study. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false-positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA. The indirect antiglobulin test was positive during Isa-Pd treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment.
Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and that SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for 5 months after the last dose. The combination of SARCLISA with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
In combination with pomalidomide and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets.
In combination with carfilzomib and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
In combination with bortezomib, lenalidomide, and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils.
Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]).
Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent serious adverse reactions in >5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%). Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).
Serious adverse reactions occurred in 71% of patients receiving Isa-VRd. The serious adverse reaction in >5% of patients who received Isa-VRd was pneumonia (30%). Fatal adverse reactions occurred in 11% of patients with Isa-VRd (those occurring in more than 1% of patients were pneumonia [5%]).
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
INDICATION
SARCLISA (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated:
-
In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
-
In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy
-
In combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Serious infusion-related reactions (IRRs), including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle.
The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone.
Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) IRR occurs and institute appropriate management.
Infections
SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia (32%).
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
SARCLISA may cause neutropenia.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%.
Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%).
In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) and in 2% of patients treated with Pd.
In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients treated with SARCLISA, carfilzomib, and dexamethasone (Isa-Kd) and in 8% of patients treated with Kd.
In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) and in 9% of patients treated with VRd.
The most common (≥1%) second primary malignancies in ICARIA-MM, IKEMA, and IMROZ (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer, except 2 patients in the Isa-VRd arm and 1 patient in the VRd arm of the IMROZ study. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false-positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA. The indirect antiglobulin test was positive during Isa-Pd treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment.
Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and that SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for 5 months after the last dose. The combination of SARCLISA with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
In combination with pomalidomide and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets.
In combination with carfilzomib and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
In combination with bortezomib, lenalidomide, and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils.
Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]).
Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent serious adverse reactions in >5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%). Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).
Serious adverse reactions occurred in 71% of patients receiving Isa-VRd. The serious adverse reaction in >5% of patients who received Isa-VRd was pneumonia (30%). Fatal adverse reactions occurred in 11% of patients with Isa-VRd (those occurring in more than 1% of patients were pneumonia [5%]).
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
INDICATION
SARCLISA (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated:
-
In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor
-
In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy
-
In combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Serious infusion-related reactions (IRRs), including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms include cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle.
The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone.
Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) IRR occurs and institute appropriate management.
Infections
SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common serious infection reported was pneumonia (32%).
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
SARCLISA may cause neutropenia.
In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%.
Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%).
In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) and in 2% of patients treated with Pd.
In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients treated with SARCLISA, carfilzomib, and dexamethasone (Isa-Kd) and in 8% of patients treated with Kd.
In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) and in 9% of patients treated with VRd.
The most common (≥1%) second primary malignancies in ICARIA-MM, IKEMA, and IMROZ (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer, except 2 patients in the Isa-VRd arm and 1 patient in the VRd arm of the IMROZ study. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false-positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA. The indirect antiglobulin test was positive during Isa-Pd treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment.
Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and that SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for 5 months after the last dose. The combination of SARCLISA with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
In combination with pomalidomide and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets.
In combination with carfilzomib and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
In combination with bortezomib, lenalidomide, and dexamethasone: The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils.
Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]).
Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent serious adverse reactions in >5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%). Adverse reactions with a fatal outcome during treatment were reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).
Serious adverse reactions occurred in 71% of patients receiving Isa-VRd. The serious adverse reaction in >5% of patients who received Isa-VRd was pneumonia (30%). Fatal adverse reactions occurred in 11% of patients with Isa-VRd (those occurring in more than 1% of patients were pneumonia [5%]).
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
This site is intended for US payers only.
© Sanofi. All rights reserved.
SARCLISA, CareASSIST, and Sanofi are registered trademarks of Sanofi or an affiliate.
