General Information

Talvey (talquetamab-tgvs) is a bispecific GPRC5D-directed CD3 T-cell engager.

Talvey is specifically 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.

Dosing/Administration

• Talvey is supplied as an injection for subcutaneous administration. 
• Administer Talvey subcutaneously according to the step-up dosing schedule below to reduce the incidence and severity of cytokine release syndrome (CRS).
•  Administer pretreatment medications prior to each dose of Talvey in the step-up dosing schedule as recommended.
• Talvey should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS).
•  Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the Talvey step-up dosing schedule.

Administer Talvey subcutaneously on a weekly or biweekly (every 2 weeks) dosing schedule according to Table 1 or Table 2. Continue treatment until disease progression or unacceptable toxicity.

Table 1: Talvey Weekly Dosing Schedule

Mechanism of Action

Talquetamab-tgvs is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D) expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as healthy tissues such as epithelial cells in keratinized tissues of the skin and tongue. In vitro, talquetamab-tgvs activated T-cells caused the release of proinflammatory cytokines and resulted in the lysis of multiple myeloma cells. Talquetamab-tgvs had anti-tumor activity in mouse models of multiple myeloma.

Side Effects

Adverse effects associated with the use of Talvey may include, but are not limited to, the following:

pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. 

 The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

The Talvey drug label comes with the following Black Box Warning: Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving Talve. Initiate Talvey treatment with step-up dosing to reduce the risk of CRS. Withhold Talvey until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur in patients receiving Talvey. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold or permanently discontinue Talvey based on severity. Talvey is available only through a restricted program called the Talvey LI and Talvey Risk Evaluation and Mitigation Strategy (REMS).

Clinical Trial Results

This indication is approved under accelerated approval based on response rate and durability of response observed in the phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation MonumenTAL-1 study involving over 300 patients. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The talquetamab Phase 2 MonumenTAL-1 study, which included patients who had received at least four prior lines of therapy and who were not exposed to prior T-cell redirection therapy (n=187), showed meaningful overall response rates (ORR).1 At the SC biweekly dose of 0.8 mg/kg, 73.6 percent of patients achieved an ORR. With a median follow-up of nearly 6 months from first response among responders, 58 percent of patients achieved a very good partial response (VGPR) or better, including 33 percent of patients achieving a complete response (CR) or better. At the SC weekly dose of 0.4 mg/kg, 73.0 percent of patients achieved an ORR. With a median follow-up of nearly 14 months from first response among responders, 57 percent of patients achieved a VGPR or better, including 35 percent of patients achieving a CR or better. Responses were durable with a median duration of response not reached in the 0.8 mg/kg SC biweekly dose group and 9.5 months in the 0.4 mg/kg SC weekly dose group. Among patients receiving the 0.8 mg/kg SC biweekly dose, an estimated 85 percent of responders maintained response for at least 9 months.

The MonumenTAL-1 study also included 32 patients who were exposed to prior bispecific antibody or CAR-T cell therapy (94 percent B-cell maturation antigen [BCMA]-directed therapy) and had received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, received Talvey at the 0.4 mg/kg SC weekly dose. With a median duration of follow-up of 10.4 months, 72 percent of patients achieved an ORR per an Independent Review Committee assessment, and an estimated 59 percent of responders maintained response for at least 9 months.