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Serious adverse reactions reported in patients included CRS (13%), pyrexia (5%), ICANS (3.8%), sepsis (3.8%), COVID-19 (3.2%), bacterial infection (2.4%), pneumonia (2.4%), viral infection (2.4%), neutropenia (2.1%) and pain (2.1%).
The most frequent adverse reactions leading to treatment discontinuation were ICANS (1.1%) and weight decreased (0.9%).
Tabulated list of adverse reactions: The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma, including patients treated with TALVEY at the recommended dosing regimen with or without prior T cell redirection therapy in MonumenTAL-1. The median duration of treatment was 7.4 (range: 0.0 to 32.9) months.
Table 12 summarises adverse reactions reported in patients who received TALVEY. The safety data of TALVEY was also evaluated in the All Treated population (N=501) with no additional adverse reactions identified.
Adverse reactions observed during clinical studies are listed as follows by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 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. (See Table 12.)
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Click on icon to see table/diagram/imageDescription of selected adverse reactions: Cytokine release syndrome: In MonumenTAL-1 (N=339), CRS occurred in 77% of patients. Most events were Grade 1 or 2, with Grade 3 events occurring in 1.5% of patients. Thirty one percent (31%) of patients experienced more than one CRS event. Most events occurred during the step-up phase following the 0.01 mg/kg dose (29%), the 0.06 mg/kg dose (44%), the 0.3 mg/kg dose (for patients who received biweekly [every 2 weeks] dosing; 33%), or the initial treatment dose (0.4 mg/kg [30%] or 0.8 mg/kg [12%]). Less than 4% of CRS events occurred from week 5 onward; all events were Grade 1. The median time to onset of CRS was 27 hours from the last dose, 91% of events occurred within 48 hours from the last dose, and the median duration was 17 hours. Tocilizumab, corticosteroids and tocilizumab in combination with corticosteroids were used to treat CRS in 39%, 5% and 3.5% of CRS events, respectively. Clinical signs and symptoms of CRS may include but are not limited to pyrexia (76%), hypotension (15%), chills (12%), hypoxia (7%), headache (4.7%), tachycardia (5%) and elevated transaminases (aspartate aminotransferase [1.5%] and alanine aminotransferase [0.9%]).
Neurologic toxicities: In MonumenTAL-1 (N=339), neurologic toxicity events were reported in 29% of patients receiving TALVEY. Neurologic toxicity events were Grade 1 (17%), Grade 2 (11%), Grade 3 (2.3%) or Grade 4 (0.3%). The most frequently reported neurologic toxicity event was headache (9%).
ICANS were only collected for Phase 2 in MonumenTAL-1. Of the 265 patients in Phase 2, ICANS occurred in 9.8% (n=26) of patients. Most events were Grade 1 or 2, with Grade 3 and 4 events occurring in 2.3% of patients. The most frequent clinical manifestation of ICANS reported were confusional state (3.8%), disorientation (1.9%), somnolence (1.9%) and depressed level of consciousness (1.9%). Sixty-eight percent (68%) were concurrent with CRS (during or within 7 days of CRS resolution). Three percent (3%) of patients experienced more than one ICANS event. In addition, one fatal ICANS event was reported in MonumenTAL-1. Most patients experienced ICANS during the step-up phase following the 0.01 mg/kg dose, the 0.06 mg/kg dose, or the initial treatment dose (0.4 mg/kg and 0.8 mg/kg) (3% each). The median time to onset of ICANS was 28 hours from the last dose, 68% of events started within 48 hours from the last dose, 32% of events occurred after 48 hours, and the median duration of ICANS was 9 hours.
Oral toxicity: In MonumenTAL-1 (N=339), 78% of patients had Grade 1 or 2 events, with Grade 3 events occurring in 2% of patients. Oral toxicity events included dysgeusia, dry mouth, dysphagia, and stomatitis were reported.
Serious infections: In MonumenTAL-1 (N=339), Grade 3 or Grade 4 infections occurred in 19% of patients; fatal infections occurred in 1.5% of patients - COVID-19 pneumonia, fungal sepsis, infection and septic shock. The most frequently reported (≥ 2%) Grade 3 or 4 infection was pneumonia. Febrile neutropenia was observed in 1% of patients with 1.2% experiencing serious febrile neutropenia. See Precautions for monitoring and management guidance.
Hypogammaglobulinaemia: Post baseline IgG values of less than 500 mg/dl consistent with hypogammaglobulinaemia have been reported in 64% of patients treated with talquetamab at the 0.4 mg/kg weekly dose schedule, 66% of patients at the 0.8 mg/kg biweekly dose schedule and in 71% of patients with prior T cell redirection therapy (see Precautions).
Skin reactions: In MonumenTAL-1 (N=339), the majority of rash cases were Grade 1 or 2, with Grade 3 events occurring in 3.5% of patients. The median time to onset from the first treatment dose for rash was 22 days. The majority of non-rash skin toxicities were Grade 1 or 2, with Grade 3 pruritus occurring in 0.3% of patients. Nail disorders occurred in 56% of patients and were Grade 1 or 2. See Precautions for management guidance.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
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