Tecvayli · 4.1 Therapeutic indications · 1

HOS-100195 · has-adverse-reaction-information · PDF-Seite 16

Summary of safety profile The most frequent adverse reactions of any grade in patients were hypogammaglobulinaemia, neutropenia, cytokine release syndrome, upper respiratory tract infection, musculoskeletal pain, diarrhoea, anaemia, cough, fatigue, injection site reaction, thrombocytopenia, pneumonia, COVID-19, lymphopenia, pyrexia, pain, nausea, headache and hypokalaemia. Serious adverse reactions were reported in 65% of patients who received TECVAYLI, including pneumonia (22%), COVID-19 (14%), cytokine release syndrome (11%), upper respiratory tract infection (7%), sepsis (6%), pyrexia (3.5%), febrile neutropenia (3.1%), diarrhoea (2.3%) and musculoskeletal pain (2.3%). Tabulated list of adverse reactions The adverse reaction frequencies are based on all-cause adverse event frequencies, from patients with multiple myeloma exposed to teclistamab, when after thorough assessment, a causal relationship between the medicinal product and the adverse event is at least a reasonable possibility. The safety data of TECVAYLI was evaluated in 739 adult patients with relapsed or refractory multiple myeloma including 165 patients from MajesTEC-1 and 291 patients from MajesTEC-9 who received subcutaneous (SC) TECVAYLI as monotherapy, with a median duration of treatment of 9 (Range 0.20 to 41) months and 13 (Range 0.10 to 28) months respectively and 283 patients from MajesTEC-3 who received SC TECVAYLI in combination with SC daratumumab with a median duration of treatment of 32 (Range 0.03 to 43) months. Table 7 summarises adverse reactions reported in patients in MajesTEC-1, MajesTEC-9 and MajesTEC-3 studies and postmarketing. Adverse reactions are listed in Table 7 by system organ class 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 order of decreasing seriousness. 16 Table 7: Adverse reactions in multiple myeloma patients treated with TECVAYLI in clinical trials and postmarketing. Frequency N=739 (all Any Grade 3 or 4 System Organ Class Ad

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HOS-100191 · has-contraindication-information · PDF-Seite 8

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 8

HOS-100190 · has-indication-information · PDF-Seite 2

TECVAYLI is indicated  in combination with daratumumab for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.  as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

HOS-100193 · has-interaction-information · PDF-Seite 15

No interaction studies have been performed with TECVAYLI. The initial release of cytokines associated with the start of TECVAYLI treatment could suppress CYP450 enzymes. The highest risk of interaction is expected to be from initiation of TECVAYLI step-up schedule up to 7 days after the first treatment dose or during a CRS event. During this time period, toxicity or medicinal product concentrations (e.g., cyclosporine) should be monitored in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index. The dose of the concomitant medicinal product should be adjusted as needed.

HOS-100194 · has-pregnancy-information · PDF-Seite 15

Women of child-bearing potential/Contraception in males and females Pregnancy status for females of child-bearing potential should be verified prior to starting treatment with TECVAYLI. Women of child-bearing potential should use effective contraception during treatment and for five months after the final dose of TECVAYLI. In clinical studies, male patients with a female partner of child-bearing potential used effective contraception during treatment and for three months after the last dose of teclistamab. Pregnancy There are no available data on the use of teclistamab in pregnant women or animal data to assess the risk of teclistamab in pregnancy. Human IgG is known to cross the placenta after the first trimester of pregnancy. Therefore, teclistamab, a humanised IgG4-based antibody, has the potential to be transmitted from the mother to the developing foetus. TECVAYLI is not recommended for women who are pregnant. TECVAYLI is associated with hypogammaglobulinaemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered. Breast-feeding It is not known whether teclistamab is excreted in human or animal milk, affects breast-fed infants or affects milk production. Because of the potential for serious adverse reactions in breast-fed infants from TECVAYLI, patients should be advised not to breast-feed during treatment with TECVAYLI and for at least five months after the last dose. 15 Fertility There are no data on the effect of teclistamab on fertility. Effects of teclistamab on male and female fertility have not been evaluated in animal studies.

HOS-100192 · has-warning-information · PDF-Seite 9

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) Cytokine release syndrome, including life-threatening or fatal reactions, may occur in patients receiving TECVAYLI. Clinical signs and symptoms of CRS may include but are not limited to fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes. Potentially life-threatening complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC). Treatment should be initiated with TECVAYLI according to the step-up dosing schedule to reduce risk of CRS. Pre-treatment medicinal products (corticosteroids, antihistamine and antipyretics) should be administered prior to each dose of the TECVAYLI step-up dosing schedule to reduce risk of CRS (see section 4.2). The following patients should be instructed to remain within proximity of a healthcare facility and monitored daily for 48 hours:  If the patient has received any dose within the TECVAYLI step-up dosing schedule (for CRS).  If the patient has received TECVAYLI after experiencing Grade 2 or higher CRS. Patients who experience CRS following their previous dose should be administered pre-treatment medicinal products prior to the next dose of TECVAYLI. Patients should be counselled to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, patients should be immediately evaluated for hospitalisation. Treatment with supportive care, tocilizumab and/or corticosteroids should be instituted, based on severity as indicated in Table 5 below. The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), has the potential to worsen CRS symptoms and should be avoided during CRS. Treatment with TECVAYLI should be withheld until CRS resolves as indicated in Table 4 (see section 4.2). Management of cytokine release syndrome CRS should be identified based on clinical presentation. Patients should be evaluated and treated for other causes of fever, hypoxia, and hypotension. If CRS is suspected, TECVAYLI should be withheld until the adverse reaction resolves (see Table 4). CRS should be managed according to the recommendations in Table 5. Supportive care for CRS (including but not limite

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