Lynozyfic · 4.4 Special warnings and precautions for use · 1

HOS-100834 · has-adverse-reaction-information · PDF-Seite 15

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%). 15 Permanent discontinuation of LYNOZYFIC due to adverse reactions occurred in 19% of patients. The most frequent adverse reactions leading to discontinuation were COVID-19 pneumonia (1.7%), Pneumocystis jirovecii pneumonia (1.7%), and pseudomonal sepsis (1.7%). Tabulated list of adverse reactions The safety population described includes 117 patients with relapsed or refractory multiple myeloma who received LYNOZYFIC at the recommended step-up treatment and full treatment dose (see section 5.1). 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. Table 8: Adverse reactions occurring in patients with multiple myeloma treated with LYNOZYFIC MedDRA System Adverse reaction Frequency Any grade Grade 3 or 4 Organ Class categories (All (%) (%) grades) Infections and Pneumoniaa Very common 32 21 infestations COVID-19 Very common 17 7 Upper respiratory tract Very common 30 2.6 infectionb

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HOS-100830 · has-contraindication-information · PDF-Seite 12

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-100829 · has-indication-information · PDF-Seite 2

LYNOZYFIC is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.

HOS-100832 · has-interaction-information · PDF-Seite 14

No drug interaction studies have been conducted with LYNOZYFIC. Transient elevation of cytokines may suppress CYP450 enzyme activities. The highest risk of drug interaction is during the step-up dosing regimen and the first full 200 mg dose in patients who are receiving concomitant CYP450 substrates. Monitor for toxicity or concentrations of medicinal 14 products that are CYP substrates where minimal changes in concentration may lead to serious adverse reactions (e.g., cyclosporine, phenytoin, sirolimus, and warfarin).

HOS-100833 · has-pregnancy-information · PDF-Seite 15

Women of childbearing potential/Contraception Pregnancy status for patients of childbearing potential should be verified prior to starting treatment with LYNOZYFIC. Patients of childbearing potential should use effective contraception during treatment with LYNOZYFIC and for at least 5 months after the last dose. Pregnancy There are no available data on the use of LYNOZYFIC in pregnant women. No animal reproductive or developmental toxicity studies have been conducted with linvoseltamab. Linvoseltamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, linvoseltamab has the potential to be transferred from the pregnant woman to the developing foetus. LYNOZYFIC is not recommended during pregnancy and in women of childbearing potential not using contraception. Based on its mechanism of action, LYNOZYFIC may cause foetal harm, including B-cell and plasma cell lymphocytopenia, when administered to a pregnant patient. Breast-feeding There is no information regarding the presence of linvoseltamab in human milk, the effects on the breastfed infant, or the effects on milk production. It is known that human IgG can be secreted in human milk. Breastfeeding should be discontinued during treatment with LYNOZYFIC and for at least 5 months after the last dose due to the potential risk for serious adverse reactions in the breastfed child. Fertility No human data on the effect of linvoseltamab on fertility are available (see section 5.3).

HOS-100831 · has-warning-information · PDF-Seite 12

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. Cytokine release syndrome (CRS) Cases of CRS have been reported in patients receiving linvoseltamab (see section 4.8). 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: 12  • 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). Immune effector cell-associated neurotoxicity syndrome (ICANS) Cases of ICANS have been reported in patients receiving linvoseltamab (see section 4.8). Clinical signs and symptoms of ICANS may include but are not limited to aphasia, cerebral oedema,

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