On August 9, 2023, the FDA accelerated the approval of talquetamab-tgvs (Talvey; Janssen Biotech), a bispecific GPRC5D-directed CD3 T-cell engager, for the treatment of adults with relapsed or refractory multiple myeloma who have previously received at least 4 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
The FDA granted this approval priority review and breakthrough and orphan drug designations.
The approval was based on efficacy results from 2 phases of the MMY1001 (MonumenTAL-1) study, a single-arm, open-label, multicenter clinical trial of 187 patients who had previously received at least 4 systemic therapies, including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
Patients received talquetamab 0.4 mg/kg subcutaneously weekly after 2 step-up doses in the first week of therapy, or talquetamab 0.8 mg/kg subcutaneously every 2 weeks after 3 step-up doses, until disease progression or unacceptable toxicity.
The main efficacy outcomes were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee using the International Myeloma Working Group criteria. The primary efficacy population included patients who had previously received at least 4 lines of therapy, including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
In the 100 patients treated with 0.4 mg/kg weekly, the ORR was 73% (95% confidence interval [CI], 63.2-81.4), and the median DOR was 9.5 months (95% CI, 6.5-not estimable). Among the 87 patients treated with 0.8 mg/kg biweekly, the ORR was 73.6% (95% CI, 63-82.4), and the median DOR was not estimable. Overall, an estimated 85% of responders maintained their response for at least 9 months.
The most common (≥20%) adverse reactions reported in the 339 patients in the safety population were cytokine release syndrome (CRS), dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
The prescribing information for talquetamab includes a boxed warning regarding serious adverse reactions associated with this drug, including life-threatening or fatal CRS and neurologic events, including immune effector cell–associated neurotoxicity syndrome (ICANS). Because of the risks for CRS and neurologic toxicity, including ICANS, talquetamab is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program called Tecvayli-Talvey REMS.
The recommended dose of talquetamab is 0.4 mg/kg weekly or 0.8 mg/kg biweekly subcutaneous injection after an initial step-up phase to determine the optimal dosing regimen for each patient.
