Prescribing information For Healthcare Professionals Only

ACTIVE INGREDIENT(S): talquetamab

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

INDICATION(S): TALVEY 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 an immunomodulatory agent, a proteasome inhibitor, and an anti CD38 antibody and have demonstrated disease progression on the last therapy.

DOSAGE & ADMINISTRATION: Treatment with TALVEY should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome (CRS) and neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

Posology: Treatment with TALVEY should be initiated according to the step-up dosing schedule (Table 1 of the SmPC) to reduce the incidence and severity of CRS. TALVEY should be given subcutaneously on a weekly or biweekly (every 2 weeks) dosing schedule. The weekly recommended subcutaneous dose on day 1 is 0.01 mg/kg, on day 3, it is 0.06 mg/kg and on day 5, it is 0.4 mg/kg, followed by a treatment dose of 0.4 mg/kg once a week thereafter. The biweekly dosing schedule on day 1 is 0.01 mg/kg, on day 3 is 0.06 mg/kg, on day 5 is 0.4 mg/kg, and on day 7 is 0.8 mg/kg, followed by a treatment dose of 0.8 mg/kg once every 2 weeks thereafter. Patients who receive talquetamab according to the 0.4 mg/kg weekly dosing schedule and have attained an adequate clinical response that is confirmed in at least two consecutive disease assessments can be considered for switch to the 0.8 mg/kg biweekly dosing schedule. Patients should be instructed to remain within proximity of a healthcare facility and monitored for 48 hours after administration of all doses within the TALVEY step-up phase for signs and symptoms of CRS and ICANS.

Duration of treatment: Patients should be treated with TALVEY until disease progression or unacceptable toxicity. Pre-treatment medicinal products: Corticosteroid, Antihistamine, Antipyretics must be administered 1 to 3 hours before each dose of TALVEY step-up dosing schedule to reduce the risk of CRS. For detailed premedication administration instructions, please refer to SmPC.

Prevention of infection: Prior to starting treatment with TALVEY, prophylaxis should be considered for the prevention of infections, per local institutional guidelines.

Dose delays: Therapy should be restarted based on recommendations in Table 2 of the SmPC, and weekly or biweekly dosing should be resumed accordingly if a dose of TALVEY is delayed.

Refer to Tables 3, 4, 5 and 6 of the SmPC for recommended dose modifications for adverse reactions following administration of TALVEY.

Paediatric population: No relevant use of TALVEY in the paediatric population.

Elderly: No dose adjustment is required.

Renal impairment: No dose adjustment for patients with mild or moderate renal impairment.

Hepatic impairment: No dose adjustment for patients with mild hepatic impairment. Limited or no data are available in patients with moderate and severe hepatic impairment.

CONTRAINDICATIONS: Refer to SmPC for hypersensitivity to the active substance or to any of the excipients.

SPECIAL WARNINGS & PRECAUTIONS: Traceability: The name and the batch number of the administered product should be clearly recorded.

Cytokine release syndrome (CRS): CRS, including life-threatening or fatal reactions, may occur in patients receiving TALVEY. 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). Patients who experience CRS following their previous dose, pretreatment medicinal products should be administered prior to the next TALVEY dose. Potential benefits of treatment should be carefully weighed against the risk of neurologic events, and heightened caution should be exercised when administering TALVEY to patients who experienced Grade 3 or higher CRS with any previous T cell redirection therapy. Counsel patients to seek medical attention if 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. Avoid the use of myeloid growth factors, particularly granulocyte macrophagecolony stimulating factor (GMCSF), during CRS. Withhold TALVEY until CRS resolves. For the management of CRS, please refer to the SmPC.

Neurologic toxicity, including ICANS: Serious or lifethreatening neurologic toxicities, including ICANS have occurred following treatment with TALVEY. 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 confusional 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 of TALVEY. For ICANS and other neurologic toxicities, TALVEY should be withheld or discontinued based on severity and management recommendations should be followed as indicated in Table 4 of SmPC. Patients should be instructed to avoid driving or operating machines during 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. For the management of Neurologic toxicities, please refer to SmPC.

Oral toxicity: Oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis occur very commonly following treatment with TALVEY. Patients should be monitored for signs and symptoms of oral toxicity and should be counselled to seek medical attention should signs or symptoms of oral toxicity occur. Supportive care may include saliva stimulating agents, steroid mouth wash, or consultation with a nutritionist. Monitor weight change during therapy and any clinically significant weight loss should be further evaluated. TALVEY 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 TALVEY. Patients should be monitored for signs and symptoms of infection prior to and during treatment with TALVEY and treated appropriately. Administer prophylactic antimicrobials according to local guidelines. Do not administer TALVEY in patients with active serious infection. TALVEY should be withheld as indicated (refer to SmPC). Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur.

Hypogammaglobulinaemia: Hypogammaglobulinaemia has been reported in patients receiving TALVEY. Immunoglobulin levels should be monitored during treatment with TALVEY. 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 were observed in patients who received TALVEY. Monitor complete blood counts at baseline and periodically during treatment. Supportive care should be provided. Patients with neutropenia should be monitored for signs of infection. Withhold TALVEY as warranted.

Skin reactions: Rash, maculopapular rash, erythema, erythematous rash, as well as nail disorders can be caused by TALVEY and should be monitored for early intervention and treatment with corticosteroids. Administer oral steroids for Grade 3 or higher, or worsening Grade 1 or 2 rashes, and consider dose modification for non-rash skin reactions. Withhold TALVEY for skin reactions and nail disorders based on severity.

Vaccines: Immune response to vaccines may be reduced when taking TALVEY. 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 TALVEY and they should use effective contraception during treatment and for 3 months after the last dose of TALVEY.

SIDE EFFECTS:
Refer to SmPC for full details on side effects.

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, Dyspnea, Oral pain, Dysgeusia, Dry mouth, Dysphagia, Diarrhoea, Stomatitis, Nausea, Constipation, Abdominal pain, Vomiting, Rash, Skin disorder, Xerosis, Pruritis, 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: Sepsis, Pneumonia, Viral infection, Haemorrhage, Febrile neutropenia, Alopecia.

Refer to the SmPC for other side effects.

PREGNANCY: Pregnancy status should be verified for females of child-bearing potential prior to initiating TALVEY. Females of reproductive potential should use effective contraception during treatment and for 3 months after the last dose of TALVEY. 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. TALVEY is not recommended for pregnant women or for women of childbearing potential not using contraception. If TALVEY is taken during pregnancy, a reduced immune response to vaccines may be expected in newborns. 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 TALVEY, patients should not breast-feed during treatment with TALVEY and for at least 3 months after the last dose.

INTERACTIONS: No interaction studies have been performed.

Talquetamab causes release of cytokines that may suppress activity of cytochrome P450 (CYP) enzymes, potentially resulting in increased exposure of CYP substrates. The highest risk of interaction is expected to occur from initiation of talquetamab step-up phase up to 9 days after the first treatment dose and during and after CRS. Monitor for toxicity or concentrations of medicinal products that are CYP substrates where minimal concentration changes may lead to serious adverse reactions. The dose of concomitant CYP substrate drugs should be adjusted as needed.

OVERDOSE: 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.

LEGAL CLASSIFICATION: Prescription Only Medicine (POM)

MARKETING AUTHORISATION NUMBER(S):
PLGB 00242/0755 (2 mg/ml), PLGB 00242/0756 (40 mg/ml)

MARKETING AUTHORISATION HOLDER:
Great Britain (PLGB): Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.

Northern Ireland (EU): Janssen-Cilag International NV Turnhoutseweg 30, B-2340 Beerse, Belgium.

FURTHER INFORMATION IS AVAILABLE FROM:
Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.

Prescribing information last revised: April 2024