Adverse reactions (≥20%) in patients receiving SARCLISA + VRd1 |
| Adverse reactions | SARCLISA + VRd (n=263) | VRd (n=181) | ||
| All grades | Grade 3 or 4 | All grades | Grade 3 or 4 | |
| Infections and infestations | ||||
| Upper respiratory tract infectiona | 65% | 4.6% | 57%b | 6% |
| Pneumoniac | 45%d | 26% | 31%e | 19% |
| COVID-19f | 22% | 0.8% | 17%g | 1.7% |
| General disorders and administration site conditions | ||||
| Fatigueh | 55% | 11% | 50% | 9% |
| Peripheral edema | 33% | 0% | 33% | 1.1% |
| IRR | 24% | 0.4% | 1.1% | 0% |
| Gastrointestinal disorders | ||||
| Diarrhea | 55% | 8% | 49% | 8% |
| Constipation | 36% | 2.3% | 41% | 1.7% |
| Nervous system disorders | ||||
| Peripheral sensory neuropathy | 54% | 7% | 61% | 6% |
| Eye disorders | ||||
| Cataract | 38% | 16% | 25% | 11% |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal paina | 38% | 4.2% | 33% | 3.3% |
| Skin and subcutaneous tissue disorders | ||||
| Rashi | 32% | 5% | 34% | 5% |
| Psychiatric disorders | ||||
| Insomnia | 22% | 3.8% | 24% | 2.2% |
- 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.2
aIncludes other related terms.1
bIncludes 1 patient (0.6%) with fatal upper respiratory tract infection.1
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.1
dIncludes 14 patients (5%) with fatal pneumonia.1
eIncludes 4 patients (2.2%) with fatal pneumonia.1
fCOVID-19 includes COVID-19 infections other than COVID-19 pneumonia.1
gIncludes 2 patients (1.1%) with fatal COVID-19.1
hFatigue includes fatigue, asthenia, or malaise.1
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.1
Serious adverse reactions1,2
- 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 TEAEs) were reported in 11% of patients with SARCLISA + VRd (that occurring in more than 1% of patients was pneumonia [5%]) vs 5.5% of patients with VRd alone
IRR=infusion-related reaction; TEAE=treatment-emergent adverse event.
Hematology laboratory abnormalities in patients receiving SARCLISA + VRd vs VRd alone1
| Laboratory parameters | SARCLISA + VRd (n=263) | VRd (n=181) | ||
| All grades | Grade 3-4 | All grades | Grade 3-4 | |
| Decreased hemoglobin | 99% | 17% | 98% | 16% |
| Decreased leukocytes | 97% | 32% | 88% | 17% |
| Decreased lymphocytes | 95% | 60% | 92% | 53% |
| Decreased platelets | 95% | 30% | 85% | 28% |
| Decreased neutrophils | 87% | 54% | 80% | 37% |
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.
Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Permanent discontinuations due to adverse events were similar across arms: 23% for SARCLISA + VRd and 26% for VRd alone.1,2
Median treatment duration1
The median treatment duration was 53 months (range: 0.5 to 69) with SARCLISA + VRd (n=263) vs 31 months (range: 0.6 to 67) for VRd alone (n=181).
Infusion-related reactions (IRRs)1
Incidence and timing of 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% experienced them 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
Symptoms of IRRs
The most common symptoms (≥5%) of an IRR across the 3 clinical trials included dyspnea and cough
- Anaphylactic reactions occurred in <1% of patients across the 3 clinical trials
Serious IRRs, including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms included cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling
Infusion interruption and discontinuation due to IRRs
Infusion interruption of SARCLISA occurred in <1% of patients across the 3 clinical trials; of these patients, 26% experienced interruptions due to IRRs
SARCLISA alone was discontinued due to IRRs in 1% of patients across the 3 clinical trials
Managing IRRs1,3 |
- 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
See the infusion rate table on the Dosing page for more details.
Defining IRR grades3 |
| Grade 1 | Mild transient reaction. |
| Grade 2 | Therapy or infusion interruption indicated, but IRR responds promptly to symptomatic treatment (eg, antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours. |
| Grade 3 | Prolonged (ie, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. |
| Grade 4 | Life-threatening consequences; urgent intervention indicated. |
IV=intravenous; NSAID=nonsteroidal anti-inflammatory drug.
Dose modifications1
Dose delay may be required to allow for recovery of blood counts in the event of hematological toxicity. For dosing instructions for combination agents administered with SARCLISA, refer to the study design description for IMROZ and the respective manufacturer’s Prescribing Information.
No dose reduction of SARCLISA is recommended
Other adverse reactions1
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 type of 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 can cause neutropenia. In 3 clinical trials, 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
- Consider the use of antibacterial and antiviral prophylaxis during treatment
- Monitor patients with neutropenia for signs of infection
- If grade 4 neutropenia occurs, delay SARCLISA dose until neutrophil count recovery to at least 1 × 109/L, and provide supportive care with growth factors, according to institutional guidelines
Second primary malignancies
- Monitor patients for the development of second primary malignancies
- The incidence of second primary malignancies is increased in patients treated with regimens that contain SARCLISA
- Across 3 clinical trials in patients treated with SARCLISA (N=592), second primary malignancies occurred in 12% of patients
- 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 - The most common (≥1%) second primary malignancies across 3 clinical trials (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 SARCLISA + VRd arm and 1 patient in the VRd arm of the IMROZ study
Laboratory test interference
SARCLISA, an anti-CD38 antibody, may interfere with blood bank serological tests with false-positive reactions in indirect antiglobulin tests (indirect Coombs tests), antibody detection (screening) tests, antibody identification panels, and antihuman globulin crossmatches in patients treated with SARCLISA. This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA.
- Conduct blood type and screen tests in patients before the first infusion of SARCLISA
- Consider phenotyping prior to starting treatment with SARCLISA
- If treatment with SARCLISA has already begun, inform the blood bank that the patient is receiving SARCLISA, and SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated red blood cells (RBCs). If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices
Important Safety Information
References: 1. SARCLISA. Prescribing information. sanofi-aventis U.S. LLC; 2024. 2. Facon T, Dimopoulos MA, Leleu XP, et al; IMROZ Study Group. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. Published online June 3, 2024. doi:10.1056/NEJMoa2400712 3. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. National Cancer Institute; 2017.
