Introduction
Talvey (talquetamab-tgvs) is a first-in-class bispecific antibody approved by the FDA in August 2023 for the treatment of relapsed or refractory multiple myeloma. This innovative therapeutic represents a significant advancement in myeloma treatment, targeting both CD3 on T-cells and GPRC5D on myeloma cells to facilitate targeted immune response against malignant plasma cells.
Mechanism of Action
Talvey is a bispecific IgG4 antibody that binds simultaneously to CD3 on cytotoxic T-cells and GPRC5D (G protein-coupled receptor family C group 5 member D) on multiple myeloma cells. This dual binding creates an immunological synapse that activates T-cells, leading to:
- T-cell mediated cytotoxicity against GPRC5D-expressing myeloma cells
- Cytokine release and T-cell proliferation
- Direct lysis of target myeloma cells
GPRC5D is highly expressed on malignant plasma cells with limited expression on normal tissues, making it an ideal therapeutic target.
Indications
Talvey is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Dosage and Administration
Step-up Dosing Schedule:- Step-up dose 1: 0.01 mg/kg subcutaneously on Day 1
- Step-up dose 2: 0.05 mg/kg subcutaneously on Day 4
- Step-up dose 3: 0.15 mg/kg subcutaneously on Day 7
- Step-up dose 4: 0.45 mg/kg subcutaneously on Day 10
- 0.8 mg/kg subcutaneously every 2 weeks OR
- 0.4 mg/kg subcutaneously weekly (based on patient response and tolerability)
- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: No dosage adjustment recommended
- Elderly: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Following subcutaneous administration, talquetamab reaches peak concentration in approximately 2-4 days. Bioavailability is approximately 70-80%. Distribution: Steady-state volume of distribution is approximately 7-10 L. Protein binding characteristics are typical of IgG antibodies. Metabolism: Talvey undergoes proteolytic catabolism via enzymatic degradation to peptides and amino acids, similar to endogenous immunoglobulins. Elimination: Elimination half-life is approximately 6-8 days. Clearance occurs primarily via target-mediated drug disposition and proteolytic pathways.Contraindications
- History of severe hypersensitivity to talquetamab-tgvs or any component of the formulation
- Active uncontrolled infection
- Concurrent use with other T-cell redirecting therapies
Warnings and Precautions
Cytokine Release Syndrome (CRS):- Occurs in approximately 77% of patients
- Most events are Grade 1-2 (76%)
- Median time to onset: 24-48 hours after dose
- Requires premedication with corticosteroids, antihistamines, and antipyretics
- Requires hospitalization for the first two step-up doses
- Includes immune effector cell-associated neurotoxicity syndrome (ICANS)
- Occurs in approximately 58% of patients
- Most events are Grade 1-2
- Monitor for cognitive changes, motor weakness, and sensory neuropathy
- Dysgeusia (63%), dry mouth (39%), dysphagia (15%)
- May require dose modifications or supportive care
- Cytopenias (neutropenia, anemia, thrombocytopenia)
- Infections (monitor for opportunistic infections)
- Skin toxicity (nail disorders, rash)
- Weight loss and decreased appetite
Drug Interactions
Immunosuppressants:- Concurrent use may increase risk of infections
- Avoid concomitant use unless medically necessary
- May alter exposure to CYP substrates due to cytokine-mediated effects on CYP enzymes
- Monitor drugs with narrow therapeutic index
- Avoid live vaccines during treatment and until immune recovery
- Inactivated vaccines may have reduced efficacy
Adverse Effects
Very Common (≥20%):- Cytokine release syndrome (77%)
- Fatigue (59%)
- Dysgeusia (63%)
- Nail disorders (51%)
- Musculoskeletal pain (47%)
- Skin disorders (45%)
- Dry mouth (39%)
- Anemia (38%)
- Neutropenia (35%)
- Diarrhea (33%)
- Hypocalcemia (32%)
- Thrombocytopenia (31%)
- Pneumonia (9%)
- Sepsis (5%)
- Hepatotoxicity (3%)
- Severe neurotoxicity (2%)
Monitoring Parameters
Prior to Each Dose:- Complete blood count with differential
- Comprehensive metabolic panel (including liver enzymes)
- Weight and nutritional status
- Neurological assessment
- Oral cavity examination
- Vital signs every 30-60 minutes
- Assessment for CRS symptoms
- Neurological monitoring
- Immunoglobulin levels
- Infection surveillance
- Response assessment (serum protein electrophoresis, free light chains, bone marrow biopsy)
- Quality of life indicators
Patient Education
Key Points for Patients:- Talvey requires subcutaneous administration in a healthcare setting for initial doses
- Report any signs of infection immediately (fever, chills, cough)
- Be aware of potential neurological symptoms (confusion, difficulty speaking, weakness)
- Maintain good oral hygiene and report any taste changes or mouth dryness
- Monitor for skin and nail changes
- Maintain adequate nutrition and hydration
- Use effective contraception during treatment and for several months after
- Carry patient wallet card identifying Talvey therapy
- Avoid alcohol-based mouthwashes if experiencing oral toxicity
- Temperature ≥38°C (100.4°F)
- Difficulty breathing or chest pain
- Severe headache or visual changes
- Confusion or difficulty speaking
- Significant skin reactions
References
1. FDA Approval Letter: Talvey (talquetamab-tgvs). August 2023. 2. Chari A, et al. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022;387(24):2232-2244. 3. ClinicalTrials.gov: MonumenTAL-1 Study (NCT03399799, NCT04634552) 4. Talvey [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2023. 5. NCCN Guidelines for Multiple myeloma. Version 3.2023. 6. Raje N, et al. Monitoring and management of adverse events associated with talquetamab therapy. Blood Adv. 2023;7(12):2876-2888. 7. European Medicines Agency Assessment Report: Talvey. October 2023.