Lynozyfic

Treatment should be initiated and supervised by physicians experienced in the treatment of multiple myeloma. 4). Prior to initiating treatment, complete blood count should be performed. 4). 6). 8). Pretreatment medicinal products should be administered until two full doses are tolerated without CRS and/or IRR.

, 500 to 1000 mg oral) 30 to 60 minutes prior to infusion Subsequent 200 mg doses • If the patient experienced CRS and/or IRR with the prior infusion, repeat pretreatment medicinal products as described above for the 2nd 200 mg dose.

• Once the 200 mg dose is tolerated without CRS and/or IRR: o If the patient received 40 mg dexamethasone IV with the prior infusion, step down to 10 mg dexamethasone IV and continue other pretreatment medicinal products as described above.

o If the patient received 10 mg dexamethasone IV with the prior infusion, discontinue all pretreatment medicinal products. Prophylactic therapy Prophylactic treatment per local institutional guidelines for Pneumocystis jirovecii pneumonia (PJP) and herpes simplex and zoster viruses is recommended for all patients.

4). 4 Recommended posology The recommended step-up treatment doses, full treatment dose, and treatment frequency are presented in Table 2. Each dose should only be administered if the previous dose is tolerated. For doses that are not tolerated, refer to Table 3, Table 4, and Table 5.

All patients should be monitored for signs and symptoms of potential CRS, IRR, and ICANS during administration and for 24 hours after the end of the infusion of the first step‑up treatment dose. 4). 4).

Table 2:

Recommended posology Dosing schedule Daya LYNOZYFIC dose Step-up dosing schedule Week 1 Day 1 Step-up treatment dose 1 5 mg Week 2 Day 1 Step-up treatment dose 2 25 mg Week 3 Day 1 First full treatment dose 200 mg Weekly dosing schedule Week 4 to Week 13 for 10 treatment doses Full treatment doses 200 mg Every 2 weeks dosing schedule Week 14 and every 2 weeks thereafter Full treatment doses 200 mg Patients who have received at least 17 doses of 200 mg and have confirmed response of very good partial response (VGPR) or better per international myeloma working group (IMWG) criteria at or after Week 24b Every 4 weeks dosing schedule At week 24 or after and every 4 weeks thereafter Treatment doses 200 mg a Weekly doses should be at least 5 days apart.

Summary of safety profile The most frequent adverse reactions were musculoskeletal pain (52%), cytokine release syndrome (46%), neutropenia (43%), cough (42%), diarrhoea (39%), anaemia (38%), fatigue (36%), pneumonia (32%), and upper respiratory tract infection (30%).

Serious adverse reactions occurred in 75% of patients who received LYNOZYFIC. The most frequent serious adverse reactions were cytokine release syndrome (27%), pneumonia (13%), COVID-19 (7%), and acute kidney injury (5%). 16 Permanent discontinuation of LYNOZYFIC due to adverse reactions occurred in 19% of patients.

7%). 1). Unless otherwise stated, the frequencies of adverse reactions in Table 8 are based on all- cause adverse event frequencies identified in 117 patients exposed to linvoseltamab during a median duration of 53 weeks (range 1, 167) in the clinical study.

Adverse reactions observed during the clinical study are listed below by MedDRA system organ class classification and by frequency. Frequency categories are defined as follows: 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) and not known (frequency cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 9 Psychiatric disorders Insomnia Very common 13 0 Nervous system disorders Encephalopathy (excl. 7 a Pneumonia includes atypical pneumonia, COVID-19 pneumonia, haemophilus infection, influenza, metapneumovirus infection, PJP, pneumonia, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, and pneumonia viral.

b Upper respiratory tract infection includes acute sinusitis, bronchitis, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, rhinovirus infection, sinobronchitis, sinusitis, upper respiratory tract infection, and viral upper respiratory tract infection.

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). CRS is a condition that may be serious or life-threatening.

Clinical signs and symptoms of CRS included, but were not limited to, pyrexia, chills, hypoxia, tachycardia, and hypotension. Administer pretreatment medicinal products (see Table 1) and initiate therapy according to LYNOZYFIC step-up dosing (see Table 2) to reduce the risk of CRS.

All patients should be monitored for signs and symptoms of CRS during and after infusion. All patients should be counselled to seek immediate medical attention should signs or symptoms of CRS occur. For the first step-up treatment dose of LYNOZYFIC, all patients should be instructed to remain with a caregiver within close proximity of the qualified treatment centre for 24 hours after the end of infusion.

For the second step-up treatment dose and subsequent doses, patients should be instructed to remain with a caregiver within close proximity of the qualified treatment centre for 24 hours after the end of infusion: 13 • For the second step-up treatment dose of LYNOZYFIC if the patient experienced CRS with the first step-up treatment dose • For a subsequent dose if the patient experienced Grade 2 CRS with the prior dose.

Patients that experience a first Grade 3 CRS event at any time should be hospitalised for 24 hours after receiving the next dose. At the first sign of CRS, patients should be immediately evaluated for hospitalisation, managed per current practice guidelines, and supportive care should be administered; LYNOZYFIC should be withheld until CRS resolves and the next dose should be modified or LYNOZYFIC should be permanently discontinued based on severity (see Table 3).

Infusion related reaction (IRR) IRR may be clinically indistinguishable from manifestations of CRS. For IRR, interrupt or slow the rate of infusion or permanently discontinue LYNOZYFIC based on severity of reaction (see Table 5). 8).

1.