Neutropenia, IRRs, pneumonia, upper respiratory tract infections, diarrhea and bronchitis were the most frequent adverse events reported in the SARCLISA® + Pd group and occurred in more than 20% of patients.
IRRs
38.2% (n=58) of patients treated with SARCLISA® in ICARIA-MM experienced an IRR.
Grade 1 IRRs were reported in 3.9%, Grade 2 in 31.6%, Grade 3 in 1.3% and Grade 4 in 1.3% of the patients treated with SARCLISA® + Pd
All patients who experienced IRRs experienced them during the first infusion.
IRRs resolved on the same day in most patients
2% (n=3) of patients also had IRRs during their second infusion; 1.3% (n=2) during their fourth infusion.
The most common symptoms of an IRR included dyspnea, cough, nasal congestion, chills and nausea. Other reported symptoms included hypertension, hypoxia, pulmonary edema, hypotension, tachycardia, syncope, bronchospasm, cytokine release syndrome, anaphylactic reaction, face edema and hyperglycemia.
SARCLISA® was discontinued in 2.6% of patients because of Grade 3 or 4 IRRs.
Median time to infusion interruption due to IRRs in ICARIA-MM: 55 minutes
No anaphylactic reactions were reported in the ICARIA-MM trial.
Across clinical trials, anaphylactic reactions have been associated with IRRs in 5 patients (0.3%). Signs and symptoms of anaphylactic reactions included bronchospasm, dyspnea, angioedema and swelling
IRR = infusion-related reaction; Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
Treatment-Emergent Adverse Events1,4
The overall incidence of serious TEAEs was 61.8% in the SARCLISA® + Pd group and 53.7% in the Pd group
Serious TEAEs (≥2% of patients) with at least a 2% higher incidence in the SARCLISA® + Pd group vs. the Pd group included infections (39.5% vs. 30.9%), febrile neutropenia (6.6% vs. 2.0%), neutropenia (3.3% vs. 1.3%) and infusion-related reactions (3.9% vs. 0%)
Fatal AEs were reported in 11.2% of patients in the SARCLISA® + Pd group and 11.4% in the Pd group
Fatal AEs reported in >1% of patients in the SARCLISA® + Pd group were pneumonia and other infections (3.3%)
TEAEs (≥5%) in patients receiving SARCLISA® + Pd with an all-grades incidence difference between groups of ≥2% (Safety Population)
Adapted from SARCLISA® Product Monograph.
*MedDRA 21.0.
†CTCAE 4.03.
‡Grade 5 neutropenia was reported in 1 patient (0.7%) in the SARCLISA® + Pd group; considered to be non-related to study treatment.
§Infusion-related reaction was a TEAE considered to be related to infusion by site investigators and with onset typically within 24 hours from the start of infusion.
¶Pneumonia includes TEAEs in the narrow SMQ infective pneumonia. Grade 5 pneumonia was reported in 1 patient (0.7%) in the Pd group and in 2 patients (1.3%) in the SARCLISA® + Pd group.
**Herpes viral infection includes the following: herpes simplex, herpes zoster, herpes zoster disseminated, oral herpes and varicella.
Note: Percentages are calculated using the number of treated patients as the denominator.
Please see the SARCLISA® Product Monograph for a complete list of adverse events.
Permanent discontinuation of treatment due to TEAEs was reported in 11 patients (7.2%) treated with SARCLISA® + Pd and in 19 patients (12.8%) treated with Pd
AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities; Pd = pomalidomide and dexamethasone; SMQ = Standard MedDRA Query; TEAE = treatment-emergent adverse event.
References
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
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, open-label, phase 3 study. Lancet. 2019;394(10214):2096–2107.
Hematologic Abnormalities and Treatment Discontinuation1
Treatment-emergent laboratory abnormalities in patients receiving SARCLISA® + Pd vs. Pd
Adapted from SARCLISA® Product Monograph.
*CTCAE version: 4.03. The denominator used for the percentage calculation was the number of patients with at least one evaluation of the laboratory test during the considered observation period.
CTCAE = Common Terminology Criteria for Adverse Events; Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
Infections1
The incidence of Grade 3 or higher infections was 42.8% in the SARCLISA® + Pd group
Pneumonia was the most commonly reported severe infection, with Grade 3 reported in 21.7% of patients in the SARCLISA® + Pd group compared with 16.1% in the Pd group, and Grade 4 in 3.3% of patients in the SARCLISA® + Pd group compared with 2.7% in the Pd group
Discontinuations of treatment due to infections were reported in 2.6% of patients in the SARCLISA® + Pd group compared with 5.4% in the Pd group
Fatal infections were reported in 3.3% of patients in the SARCLISA® + Pd group and 4.0% in the Pd group
Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
Warnings and Precautions: Neutropenia1
Grade 3 and 4 neutropenia were reported as laboratory abnormalities in 24.3% and 60.5% of patients treated with SARCLISA® + Pd
Neutropenic complications included febrile neutropenia and neutropenic infections (11.8% and 25% of patients, respectively)
SARCLISA® infusion was omitted due to neutropenia in 9.2% of patients and Pd dose reduction or omission due to neutropenia occurred in 29.6% and 9.2% of patients, respectively
Use of G-CSF was required in 69.1% of the patients, either for prophylaxis or as treatment for neutropenia
Monitor complete blood cell counts at baseline and periodically during treatment
Antibacterial, antifungal and antiviral prophylaxis can be considered during treatment
Monitor patients with neutropenia for signs of infection
SARCLISA® dose delays, modification of pomalidomide and dexamethasone treatment, and the use of G-CSF may be required to allow improvement of neutrophil count
Dose Adjustment
No dose reductions of SARCLISA® are recommended
In case of Grade 3 and Grade 4 neutropenia, SARCLISA® administration should be delayed until neutrophil count improves to at least 1.0 x 109/L
The use of colony-stimulating factors (e.g., G-CSF) should be considered according to local guidelines
Temporary interruption or definitive discontinuation of SARCLISA® treatment may be required for neutropenia
G-CSF = granulocyte colony-stimulating factor; Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
IRR = infusion-related reaction; Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities; Pd = pomalidomide and dexamethasone; SMQ = Standard MedDRA Query; TEAE = treatment-emergent adverse event.
References
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
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, open-label, phase 3 study. Lancet. 2019;394(10214):2096–2107.
CTCAE = Common Terminology Criteria for Adverse Events; Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
G-CSF = granulocyte colony-stimulating factor; Pd = pomalidomide and dexamethasone.
Reference
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
SARCLISA® (isatuximab for injection) is indicated:
in combination with pomalidomide and dexamethasone, for the treatment of patients with relapsed and refractory multiple myeloma who have received at least two 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.
Important Safety Information
Clinical use:
SARCLISA® is not indicated in pediatric patients (<18 years of age). No overall differences in safety and efficacy were observed between older (≥65 years of age) and younger patients.
Contraindications:
Hypersensitivity to SARCLISA® or any ingredient in the formulation or any of its components.
Most serious warnings and precautions:
Neutropenia: Neutropenia occurred as a laboratory abnormality in 54.8% of patients treated with SARCLISA® in combination with carfilzomib and dexamethasone, with Grade 3–4 neutropenia reported as a laboratory abnormality in 19.2% of patients (Grade 3 in 17.5%, Grade 4 in 1.7%). Neutropenic complications occurred in 2.8% of patients, including febrile neutropenia (1.1%) and neutropenic infections (1.7%). Grade 3 and 4 neutropenia occurred as laboratory abnormalities in 24.3% and 60.5% of patients treated with SARCLISA® in combination with pomalidomide and dexamethasone. Neutropenic complications included febrile neutropenia (11.8% of patients) and neutropenic infections (25% of patients). Monitor complete blood cell counts at baseline and periodically during treatment. Monitor patients with neutropenia for signs of infection.
Infusion-related reactions (IRRs): IRRs, mostly Grade 1 or 2, were reported in 81 patients (45.8%) treated with SARCLISA® in combination with carfilzomib and dexamethasone (Grade 1 in 13.6%, Grade 2 in 31.6%, Grade 3 in 0.6%); IRRs occurred on the infusion day in 99.2% of episodes. 94.4% of those experiencing an IRR experienced it during the first cycle of treatment. All IRRs resolved, with 73.8% of IRRs resolving on the same day they were experienced, 23.8% resolving the day after, and 2.5% resolving after more than 2 days. IRRs, mostly Grade 1 or 2, were observed in 38.2% of patients treated with SARCLISA® in combination with pomalidomide and dexamethasone. All IRRs started during the first SARCLISA® infusion and resolved on the same day in most patients. To decrease the risk and severity of IRRs, patients should be premedicated prior to the SARCLISA® infusion. Vital signs should be frequently monitored during the entire SARCLISA® infusion. In the event of an IRR in which infusion interruption or intervention (Grade 2) is indicated, interrupt the SARCLISA® infusion and provide appropriate medical and supportive measures. If symptoms improve to Grade ≤1, restart SARCLISA® infusion at half 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 per the Infusion Rates of SARCLISA® Administration, consistent with the Product Monograph. If symptoms do not improve to Grade ≤1 after interruption of SARCLISA® infusion, persist or worsen despite appropriate medications, require hospitalization or are life-threatening (Grade 3 or 4), permanently discontinue SARCLISA® and institute appropriate management. SARCLISA® may cause serious infusion reactions, including anaphylactic reactions. Signs and symptoms of anaphylactic reactions include bronchospasm, dyspnea, angioedema and swelling.
Other relevant warnings and precautions:
Interference with serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) assays
Interference with indirect antiglobulin test
Driving and operating machinery
Fertility
Pregnancy and breastfeeding
Second primary malignancies
Tumour lysis syndrome
For more information:
Please consult the Product Monograph at http://products.sanofi.ca/en/sarclisa-en.pdf for important information relating to the adverse events, drug interactions and dosing information that have not been discussed in this piece.
The Product Monograph is also available by calling Sanofi Canada Medical Information at 1-800-589-6215.
The content of the website you are visiting is not controlled by the sarclisa.ca team. The link is being offered for your convenience and should not be viewed as an endorsement of the content, product or services offered here.
SARCLISA® (isatuximab for injection) is indicated:
in combination with pomalidomide and dexamethasone, for the treatment of patients with relapsed and refractory multiple myeloma who have received at least two 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.
Important Safety Information
Clinical use:
SARCLISA® is not indicated in pediatric patients (<18 years of age). No overall differences in safety and efficacy were observed between older (≥65 years of age) and younger patients.
Contraindications:
Hypersensitivity to SARCLISA® or any ingredient in the formulation or any of its components.
Most serious warnings and precautions:
Neutropenia: Neutropenia occurred as a laboratory abnormality in 54.8% of patients treated with SARCLISA® in combination with carfilzomib and dexamethasone, with Grade 3–4 neutropenia reported as a laboratory abnormality in 19.2% of patients (Grade 3 in 17.5%, Grade 4 in 1.7%). Neutropenic complications occurred in 2.8% of patients, including febrile neutropenia (1.1%) and neutropenic infections (1.7%). Grade 3 and 4 neutropenia occurred as laboratory abnormalities in 24.3% and 60.5% of patients treated with SARCLISA® in combination with pomalidomide and dexamethasone. Neutropenic complications included febrile neutropenia (11.8% of patients) and neutropenic infections (25% of patients). Monitor complete blood cell counts at baseline and periodically during treatment. Monitor patients with neutropenia for signs of infection.
Infusion-related reactions (IRRs): IRRs, mostly Grade 1 or 2, were reported in 81 patients (45.8%) treated with SARCLISA® in combination with carfilzomib and dexamethasone (Grade 1 in 13.6%, Grade 2 in 31.6%, Grade 3 in 0.6%); IRRs occurred on the infusion day in 99.2% of episodes. 94.4% of those experiencing an IRR experienced it during the first cycle of treatment. All IRRs resolved, with 73.8% of IRRs resolving on the same day they were experienced, 23.8% resolving the day after, and 2.5% resolving after more than 2 days. IRRs, mostly Grade 1 or 2, were observed in 38.2% of patients treated with SARCLISA® in combination with pomalidomide and dexamethasone. All IRRs started during the first SARCLISA® infusion and resolved on the same day in most patients. To decrease the risk and severity of IRRs, patients should be premedicated prior to the SARCLISA® infusion. Vital signs should be frequently monitored during the entire SARCLISA® infusion. In the event of an IRR in which infusion interruption or intervention (Grade 2) is indicated, interrupt the SARCLISA® infusion and provide appropriate medical and supportive measures. If symptoms improve to Grade ≤1, restart SARCLISA® infusion at half 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 per the Infusion Rates of SARCLISA® Administration, consistent with the Product Monograph. If symptoms do not improve to Grade ≤1 after interruption of SARCLISA® infusion, persist or worsen despite appropriate medications, require hospitalization or are life-threatening (Grade 3 or 4), permanently discontinue SARCLISA® and institute appropriate management. SARCLISA® may cause serious infusion reactions, including anaphylactic reactions. Signs and symptoms of anaphylactic reactions include bronchospasm, dyspnea, angioedema and swelling.
Other relevant warnings and precautions:
Interference with serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) assays
Interference with indirect antiglobulin test
Driving and operating machinery
Fertility
Pregnancy and breastfeeding
Second primary malignancies
Tumour lysis syndrome
For more information:
Please consult the Product Monograph at http://products.sanofi.ca/en/sarclisa-en.pdf for important information relating to the adverse events, drug interactions and dosing information that have not been discussed in this piece.
The Product Monograph is also available by calling Sanofi Canada Medical Information at 1-800-589-6215.
