August 2023: Talquetamab-tgvs (Talvey, Janssen Biotech, Inc.) has been given accelerated approval by the Food and Drug Administration for the treatment of adults with relapsed or refractory multiple myeloma who have undergone at least four prior lines of therapy, including proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody.
A single-arm, open-label, multicenter research called MMY1001 (MonumenTAL-1) (NCT03399799, NCT4634552) that included 187 patients who had previously had at least four systemic medications assessed the efficacy of the treatment. Following two step-up doses in the first week of therapy, patients received talquetamab-tgvs 0.4 mg/kg subcutaneously weekly or talquetamab-tgvs 0.8 mg/kg subcutaneously biweekly (every two weeks), following three step-up doses, until disease progression or intolerable toxicity.
Overall response rate (ORR) and duration of response (DOR), which were evaluated by an independent review committee based on IMWG guidelines, were the primary efficacy outcome measures. Patients who had previously had at least four lines of therapy, such as a proteasome inhibitor, an immunomodulator, and an anti-CD38 monoclonal antibody, made up the primary efficacy population. The median DOR was 9.5 months (95% CI: 6.5, not estimable) and the ORR in the 100 patients taking 0.4 mg/kg weekly was 73% (95% confidence interval (CI): 63.2%, 81.4%). The median DOR in the 87 patients taking 0.8 mg/kg biweekly was not estimable, while the ORR was 73.6% (95% CI: 63%, 82.4%). About 85% of respondents reportedly continued to respond for at least nine months.
A Boxed Warning for immunological effector cell-associated neurotoxicity (ICANS) and neurologic toxicity, including life-threatening or lethal cytokine release syndrome (CRS), is included in the prescribing material for talquetamab-tgvs. Talquetamab-tgvs is only offered in a restricted programme under a Risk Evaluation and Mitigation Strategy (REMS), known as the Tecvayli-Talvey REMS, due to the risks of CRS and neurologic toxicity, including ICANS.
The 339 patients in the safety population experienced CRS, dysgeusia, nail disorder, musculoskeletal discomfort, skin disorder, rash, exhaustion, loss of weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, diarrhoea, and adverse events in that order ( 20%).
Talquetamab-tgvs should be administered at a dose of either 0.4 mg/kg weekly or 0.8 mg/kg biweekly. The complete dose schedules are listed in the prescribing information.