Sarclisa

SARCLISA should be administered by a healthcare professional, in an environment where resuscitation facilities are available. Premedication 3 Prevention of infusion reaction Premedication should be used prior to SARCLISA infusion with the following medicinal products to reduce the risk and severity of infusion reactions: • Dexamethasone 40 mg oral or intravenous (or 20 mg oral or intravenous for patients ≥ 75 years of age): when administered in combination with isatuximab and pomalidomide, Dexamethasone 20 mg (intravenous on the days of isatuximab and/or carfilzomib infusions, and oral on the other days): when administered in combination with isatuximab and carfilzomib.

Dexamethasone 20 mg (intravenous on the days of isatuximab infusion, and oral on the other days): when administered in combination with isatuximab, bortezomib, and lenalidomide. • Montelukast 10 mg oral (or equivalent), at least at cycle 1.

• Acetaminophen 650 mg to 1 000 mg oral (or equivalent). , omeprazole, esomeprazole). , cetirizine, promethazine, dexchlorpheniramine]). The intravenous use is preferred for at least the first 4 infusions. The above recommended dose of dexamethasone (oral or intravenous) corresponds to the total dose to be administered only once before the infusion, as part of the premedication and the backbone treatment, before isatuximab and pomalidomide, before isatuximab and carfilzomib, and before isatuximab, bortezomib, and lenalidomide administration.

The recommended premedication agents should be administered 15-60 minutes prior to starting a SARCLISA infusion. Patients who do not experience an infusion reaction upon their first 4 administrations of SARCLISA may have their need for subsequent premedication reconsidered.

g. G-CSF) should be considered to mitigate the risk of neutropenia. 4). 4). Posology The recommended dose of SARCLISA is 10 mg/kg body weight administered as an intravenous infusion in combination with pomalidomide and dexamethasone (Isa-Pd) or in combination with carfilzomib and dexamethasone (Isa-Kd), or in combination with bortezomib, lenalidomide, and dexamethasone (Isa-VRd).

SARCLISA dosing schedules are provided in Tables 1, 2, and 3:

Table 1: SARCLISA dosing schedule in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone Cycles Dosing schedule Cycle 1 (28-day cycle) Days 1, 8, 15 and 22 (weekly) Cycle 2 and beyond (28-day cycle) Days 1, 15 (every 2 weeks) 4 Each treatment cycle consists of a 28-day period.

7 %). 8 % of patients receiving Isa-Pd. 6 %). 2 % of patients treated with Isa-Pd. 0 % of patients). 0 %). 3 % of patients receiving Isa-Kd. 5 %). 5 % of patients treated with Isa-Kd. 1 % of patients). 1%). 7% of patients receiving Isa-VRd. 7%, including Covid-19 pneumonia).

5% of patients. 8% of patients treated with Isa-VRd. 4%). 2% of patients receiving Isa-VRd. 1%). 3% of patients). Permanent discontinuation of treatment because of adverse reactions was reported in 3% of patients treated with Isa-VRd. Tabulated list of adverse reactions 11 Adverse reactions are described using the NCI Common Toxicity Criteria, the COSTART and the MedDRA terms.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); frequency not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

1) and post-market settings. 0 % 12 a The term pneumonia is a grouping of the following terms: atypical pneumonia, bronchopulmonary aspergillosis, pneumonia, pneumonia haemophilus, pneumonia influenza, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, pneumonia bacterial, haemophilus infection, lung infection, pneumonia fungal and pneumocystis jirovecii pneumonia.

b See “Description of selected adverse reactions”. c Based on second primary malignancies reported during study treatment period and during post-treatment period. d Based on post-marketing adverse reactions.

Table 6a:

Adverse reactions reported in patients with multiple myeloma treated with isatuximab in combination with carfilzomib and dexamethasone System Organ Class Preferred Term Adverse reaction Frequency Incidence (N = 177) Any Grade Grade ≥ 3 […]

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 8). In ICARIA-MM, all infusion reactions started during the first SARCLISA infusion and resolved on the same day in 98 % of the infusions.

The most common symptoms of an infusion reaction included dyspnoea, cough, chills and nausea. The most common severe signs and symptoms included hypertension, dyspnoea, and bronchospasm. 2 % of episodes. 4 % of those experiencing an IR experienced it during the first cycle of treatment.

All infusion reactions resolved. The most common symptoms of an infusion reaction included cough, dyspnoea, nasal congestion, vomiting and nausea. The most common severe signs and symptoms included hypertension and dyspnoea. 3% of patients.

All IRs resolved. The most common symptoms of an IR included dyspnoea and chills. The most common severe sign and symptom was hypertension. 4% at the subsequent infusions. All IRs resolved. 8). 8). 2). Vital signs should be frequently monitored during the entire SARCLISA infusion.

2). In case symptoms do not improve to grade ≤ 1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medicinal products, require hospitalization or are life- threatening, permanently discontinue SARCLISA and institute appropriate management.

4 % of patients. 0 % of neutropenic infections. 0 % of patients. 7 % of neutropenic infections. 6% Grade 4) and as an adverse reaction in 30% of patients. 6% of neutropenic infection. 8). Complete blood cell counts should be monitored periodically during treatment.

Patients with neutropenia should be monitored for signs of infection. No dose reductions of SARCLISA are recommended. g. 2). (1) Haematology laboratory values were recorded as adverse reactions only if they led to treatment discontinuation and/or dose modification and/or fulfilled a serious criterion.

1.