TALVEY

/ J-C Health Care Ltd

Administer weekly or biweekly (every 2 weeks) by subcutaneous injection. Patients should be instructed to remain within proximity of a healthcare facility and monitored, for 48 hours after each dose during the step-up phase of this medical product for signs and symptoms of CRS and ICANS.
Duration of treatment
Patients should be treated with Talquetamab until disease progression or unacceptable toxicity.
Pre-treatment
The following pre-treatment medicinal products must be administered 1 to 3 hours before each dose during the step-up phase to reduce the risk of CRS.
• Corticosteroid (oral or intravenous dexamethasone 16 mg or equivalent)
• Antihistamine (oral or intravenous diphenhydramine 50 mg or equivalent)
• Antipyretics (oral or intravenous paracetamol 650 mg to 1 000 mg or equivalent)
Pre-treatment medications should be administered prior to subsequent doses in patients who repeat doses during the step-up phase due to dose delays or in those who have experienced CRS.
See prescribing information for full details.

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

Hypersensitivity to the active substance or to any of the excipients

Cytokine release syndrome (CRS)
CRS, including life-threatening or fatal reactions, may occur in patients receiving this medical product. Clinical signs and symptoms of CRS may include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, tachycardia and elevated transaminases. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
Therapy should be initiated with step-up phase dosing and pre-treatment medicinal products (corticosteroids, antihistamine, and antipyretics) should be administered prior to each dose during the step-up phase to reduce the risk of CRS. Patients should be monitored following administration accordingly. In patients who experience CRS following their previous dose, pre-treatment medicinal products should be administered prior to the next dose.
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 and treatment with supportive care, tocilizumab and/or corticosteroids, should be instituted based on severity. The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), should be avoided during CRS. Talquetamab should be withheld until CRS resolves.
Neurologic toxicity, including ICANS
ICANS, including fatal reactions, have occurred following treatment with this medical product. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confessional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.
Patients should be monitored for signs and symptoms of neurologic toxicities and treated promptly. Patients should be counselled to seek medical attention should signs or symptoms of neurologic toxicities including ICANS occur. At the first sign of neurologic toxicities including ICANS, the patient should be immediately evaluated and supportive care should be provided based on severity. Patients who experience Grade 2 or higher ICANS should be instructed to remain within proximity of a healthcare facility and monitored for signs and symptoms for 48 hours following the next dose.
Due to the potential for ICANS, patients should be instructed to avoid driving or operating machines during the step-up phase and for 48 hours after completion of the step-up phase, and in the event of new onset of any neurological symptoms, until symptoms resolve.
Management of neurologic toxicities
At the first sign of neurologic toxicity, including ICANS, neurology evaluation should be considered. Other causes of neurologic symptoms should be ruled out. This medical product should be withheld until adverse reaction resolves. Intensive care and supportive therapy should be provided for severe or life-threatening neurologic toxicities.
Oral toxicity
Oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis occur very commonly following treatment with Talquetamab.
Patients should be monitored for signs and symptoms of oral toxicity. Patients should be counselled to seek medical attention should signs or symptoms of oral toxicity occur, and supportive care should be provided. Supportive care may include saliva stimulating agents, steroid mouth wash, or consultation with a nutritionist. This medical product should be interrupted or less frequent dosing should be considered.
Over time, notable weight loss may occur. Weight change should be monitored regularly during therapy. Clinically significant weight loss should be further evaluated. Talquetamab should be interrupted or less frequent dosing should be considered.
Serious infections
Serious infections, including life-threatening or fatal infections, have been reported in patients receiving Talquetamab. Patients should be monitored for signs and symptoms of infection prior to and during treatment with Talquetamab and treated appropriately. Prophylactic antimicrobials should be administered according to local guidelines. This medical product should not be administered in patients with active serious infection. Talquetamab should be withheld as indicated. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur.
Hypogammaglobulinaemia
Immunoglobulin levels should be monitored during treatment. Intravenous or subcutaneous immunoglobulin therapy was used to treat hypogammaglobulinaemia patients. Patients should be treated according to local institutional guidelines, including infection precautions, antibiotic or antiviral prophylaxis, and administration of immunoglobulin replacement.
Cytopenias
Treatment-emergent Grade 3 or 4 neutropenia, febrile neutropenia and thrombocytopenia have been observed in patients who received Talquetamab. A majority of cytopenias occurred during the first 8 to 10 weeks. Complete blood counts should be monitored at baseline and periodically during treatment. Patients with neutropenia should be monitored for signs of infection. This medical product should be withheld as warranted.
Skin reactions
Talquetamab can cause skin reactions including rash, erythema, palmar-plantar erythrodysesthesia syndrome, as well as nail disorders. Skin reactions including rash progression should be monitored for early intervention and treatment with corticosteroids. For Grade 3 or higher, or worsening Grade 1 or 2 rashes, oral steroids should also be administered. For non-rash skin reactions dose modification may be considered. For skin reactions and nail disorders, this medical product should be withheld.
Vaccines
Immune response to vaccines may be reduced when taking Talquetamab. The safety of immunisation with live viral vaccines during or following Talquetamab treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment, and at least 4 weeks after treatment.
Women of child-bearing potential/contraception
Pregnancy status of females of child-bearing potential should be verified prior to initiating treatment with Talquetamab. Females of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.
See prescribing information for full details.

Very common: Bacterial infection, Fungal infection, COVID-19, Upper respiratory tract infection, Neutropenia, Anaemia, Thrombocytopenia, Lymphopenia, Leukopenia, Cytokine release syndrome, Hypogammaglobulinaemia, Decreased appetite, Hypokalaemia, Hypophosphataemia, Hypomagnesaemia, Immune effector cell-associated neurotoxicity syndrome, Encephalopathy, Headache, Motor dysfunction, Dizziness, Sensory neuropathy, Cough, Dyspnoea, Dysgeusia, Dry mouth, Dysphagia, Diarrhoea, Stomatitis, Nausea, Constipation, Oral pain, Abdominal pain, Vomiting, Rash, Skin disorder, Xerosis, Pruritus, Nail disorder, Musculoskeletal pain, Fatigue, Weight decreased, Pyrexia, Pain, Oedema, Injection site reaction, Chills, Fibrinogen decreased, aPTT prolonged, Transaminase elevation, INR increased, Gamma-glutamyltransferase increased.
Common: Palmar-plantar erythrodysesthesia syndrome, Alopecia
See prescribing information for full details.

No interaction studies have been performed.
See prescribing information for full details.

Women of childbearing potential/Contraception in females: Pregnancy status of females of child-bearing potential should be verified prior to initiating treatment. Females of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.
Pregnancy: There are no available data on the use of Talquetamab in pregnant women or animal data to assess the risk of Talquetamab in pregnancy. Human IgG is known to cross the placenta after the first trimester of pregnancy. Therefore, talquetamab has the potential to be transmitted from the mother to the developing foetus. The effects of Talquetamab on the developing foetus are unknown. This medical product is not recommended for women who are pregnant or for women of childbearing potential not using contraception.
If Talquetamab is taken during pregnancy, a reduced immune response to vaccines may be expected in newborns. Consequently, newborn vaccinations with live vaccines such as BCG vaccine should be postponed until 4 weeks.
Lactation: It is not known whether talquetamab is excreted in human milk. Because the potential for serious adverse reactions in breast-fed infants is unknown for this medical product, patients should not breast-feed during treatment and for at least 3 months after the last dose.
See prescribing information for full details.

The maximum tolerated dose of talquetamab has not been determined. In clinical studies, doses of up to 1.2 mg/kg once every 2 weeks and 1.6 mg/kg every month have been administered.
In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse effects and appropriate symptomatic treatment should be instituted immediately.

Talquetamab has major influence on the ability to drive and use machines.
Due to the potential for ICANS, patients receiving Talquetamab are at risk of depressed level of consciousness. Patients should be instructed to avoid driving or operating machines during the step-up phase and for 48 hours after completion of the step-up phase, and in the event of new onset of any neurological symptoms, until symptoms resolve.