Select Secondary Endpoints: Time to response, duration of response
*Comparative clinical significance is unknown.
†PFS results were assessed by an IRC based on central laboratory data for M-protein and a central radiologic imaging review using the IMWG criteria.
‡sCR, CR, VGPR and PR were evaluated by an IRC using the IMWG response criteria (2016).
CD38 = cluster of differentiation 38; CR = complete response; IMWG = International Myeloma Working Group; IRC = Independent Response Committee; IV = intravenous; ORR = overall response rate; Pd = pomalidomide and dexamethasone; PFS = progression-free survival; PI = proteasome inhibitor; PO = by mouth; PR = partial response; sCR = stringent complete response; VGPR = very good partial response.
References
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 1.2022.
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.
Patient Population1,4
Patient groups were stratified by age (<75 years vs. ≥75 years) and number of previous lines of therapy (2 or 3 vs. >3).
Baseline demographics and patient characteristics of the intention-to-treat population
Adapted from Attal et al. 2019.
Data are median (IQR) or n (%). ISS stage at study entry, not at diagnosis, was used for efficacy assessments.
*Information on race could not be collected in some countries; hence, not all values were available.
†IgM unknown or undetected.
COPD = chronic obstructive pulmonary disease; eGFR = estimated glomerular filtration rate; IgA = immunoglobulin A; IgG = immunoglobulin G; IgM = immunoglobulin M; IQR = interquartile range; ISS = International Staging System, derived based on the combination of serum β2, macroglobulin and albumin; ORR = overall response rate; Pd = pomalidomide and dexamethasone; PFS = progression-free survival.
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.
PFS Results1,4
Significantly Prolonged PFS Demonstrated with SARCLISA® + Pd Group vs. Pd Group1,4
Adapted from Attal et al. 2019.
PFS results were assessed by an IRC based on central laboratory data for M-protein and a central radiologic imaging review using the IMWG criteria (2016).
40% reduction in the instantaneous risk of progression or death in the SARCLISA® + Pd group vs. Pd group (HR*=0.596; 95% CI: 0.44–0.81; P=0.001)1,4
OS was analyzed at a preplanned interim analysis when the primary analyses for PFS and ORR were conducted. OS was not mature at the time of the interim analysis. At the pre-planned primary OS analysis, conducted after 220 events had occurred (median follow-up time of 51.09 months), median OS was estimated to be 24.6 months in the Isa-Pd group and 17.7 months in the Pd group (HR=0.776; 95% CI: 0.594 to 1.015). The results did not achieve statistical significance.
Subgroup analyses based on PFS HR were generally consistent with those of the primary PFS analysis across the pre-defined subgroups, including patients with high-risk cytogenetics, >75 years of age, with ISS stage III at study entry, with baseline creatinine clearance <60 mL/min/1.73 m², with >3 prior lines of therapy, refractory to lenalidomide or proteasome inhibitor, and refractory to lenalidomide at the last line before the study entry.†,1,4
Adapted from Attal et al. 2019.
Subgroup analyses based on PFS HR that did not show significant results were as follows:
Adapted from Attal et al. 2019.
*Stratified by age (<75 years vs. ≥75 years) and number of previous lines of therapy (2 or 3 vs. >3) according to log-rank test. The p-value for PFS was derived based on stratified log-rank test. A predefined hierarchical procedure allows for testing of an endpoint only when the previous one is statistically significant, in the following order: PFS, ORR and OS.
†High-risk cytogenetics is defined as central laboratory cutoff of 50% for del(17p), 30% for t(4;14) and t(14;16).
CI = confidence interval; HR = hazard ratio; IMWG = International Myeloma Working Group; IRC = Independent Response Committee; ISS = International Staging System; MDRD = modification of diet in renal disease; ORR = overall response rate; OS = overall survival; Pd = pomalidomide and dexamethasone; PFS = progression-free survival.
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.
ORR1,4
ORR Data in SARCLISA® + Pd Group vs. Pd Group
An improvement in ORR was seen in the SARCLISA® + Pd group (60.4%, n=93/154; CI: 0.522–0.682) vs. the Pd group (35.3%, n=54/153; CI: 0.278–0.434, P<0.0001).*
Adapted from Attal et al. 2019.
*sCR, CR, VGPR and PR were evaluated by an IRC using IMWG response criteria (2016).
†95% CI estimated using Clopper-Pearson method.
‡Stratified by age (<75 years vs. ≥75 years) and number of previous lines of therapy (2 or 3 vs. >3) according to interactive response technology. Predefined hierarchical procedure allows for testing of an endpoint only when the previous one is statistically significant, in the following order: PFS, ORR and OS.
CI = confidence interval; CR = complete response; IMWG = International Myeloma Working Group; IRC = Independent Response Committee; ORR = overall response rate; OS = overall survival; Pd = pomalidomide and dexamethasone; PFS = progression-free survival; PR = partial response; sCR = stringent complete response; VGPR = very good partial response.
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.
Time to Response1,4
The median time to first response was 35 days in the SARCLISA® + Pd group vs. 58 days in the Pd group.
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.
Duration of Response1,4
The median duration of response was 13.3 months (95% CI: 10.6–NR) in the SARCLISA® + Pd group vs. 11.0 months (95% CI: 8.5–NR) in the Pd group.
Adapted from SARCLISA® Product Monograph.
CI = confidence interval; NR = not reached; ORR = overall response rate; Pd = pomalidomide and dexamethasone; PFS = progression-free survival.
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.
*Comparative clinical significance is unknown.
†PFS results were assessed by an IRC based on central laboratory data for M-protein and a central radiologic imaging review using the IMWG criteria.
‡sCR, CR, VGPR and PR were evaluated by an IRC using the IMWG response criteria (2016).
CD38 = cluster of differentiation 38; CR = complete response; IMWG = International Myeloma Working Group; IRC = Independent Response Committee; IV = intravenous; ORR = overall response rate; Pd = pomalidomide and dexamethasone; PFS = progression-free survival; PI = proteasome inhibitor; PO = by mouth; PR = partial response; sCR = stringent complete response; VGPR = very good partial response.
References
PrSARCLISA® Product Monograph. Sanofi Canada. January 12, 2024.
NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 1.2022.
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.
COPD = chronic obstructive pulmonary disease; eGFR = estimated glomerular filtration rate; IgA = immunoglobulin A; IgG = immunoglobulin G; IgM = immunoglobulin M; IQR = interquartile range; ISS = International Staging System, derived based on the combination of serum β2, macroglobulin and albumin; ORR = overall response rate; Pd = pomalidomide and dexamethasone; PFS = progression-free survival.
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.
*Stratified by age (<75 years vs. ≥75 years) and number of previous lines of therapy (2 or 3 vs. >3) according to log-rank test. The p-value for PFS was derived based on stratified log-rank test. A predefined hierarchical procedure allows for testing of an endpoint only when the previous one is statistically significant, in the following order: PFS, ORR and OS.
†High-risk cytogenetics is defined as central laboratory cutoff of 50% for del(17p), 30% for t(4;14) and t(14;16).
CI = confidence interval; HR = hazard ratio; IMWG = International Myeloma Working Group; IRC = Independent Response Committee; ISS = International Staging System; MDRD = modification of diet in renal disease; ORR = overall response rate; OS = overall survival; Pd = pomalidomide and dexamethasone; PFS = progression-free survival.
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.
*sCR, CR, VGPR and PR were evaluated by an IRC using IMWG response criteria (2016).
†95% CI estimated using Clopper-Pearson method.
‡Stratified by age (<75 years vs. ≥75 years) and number of previous lines of therapy (2 or 3 vs. >3) according to interactive response technology. Predefined hierarchical procedure allows for testing of an endpoint only when the previous one is statistically significant, in the following order: PFS, ORR and OS.
CI = confidence interval; CR = complete response; IMWG = International Myeloma Working Group; IRC = Independent Response Committee; ORR = overall response rate; OS = overall survival; Pd = pomalidomide and dexamethasone; PFS = progression-free survival; PR = partial response; sCR = stringent complete response; VGPR = very good partial response.
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.
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.
CI = confidence interval; NR = not reached; ORR = overall response rate; Pd = pomalidomide and dexamethasone; PFS = progression-free survival.
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.
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.
