Of the 143 patients in the lower-dose group of the MonumenTAL-1 trial, roughly three in four responded to talquetamab. They had all run through most of what myeloma medicine offers. In August 2023 the US Food and Drug Administration used that result to grant the drug accelerated approval, and Janssen announced it as Talvey.
The label is narrow. Talvey is for adults whose multiple myeloma has returned or stopped responding after at least four earlier lines of treatment. Those must have included three drug types: a proteasome inhibitor, an immune-modulating agent, plus an anti-CD38 antibody. The International Myeloma Foundation calls it the first bispecific antibody cleared by the FDA that hits the targets GPRC5D and CD3. BioSpace counts it as only the second bispecific cleared for myeloma of any kind.
Two arms, one handshake
The design is simple to describe. One arm of the antibody grips GPRC5D, a protein found on myeloma cells. The other grips CD3 on the patient’s own T cells. Once the two are joined, the T cell releases toxic granules and kills the cancer cell.
That makes it a different kind of treatment from CAR T-cell therapy. Nothing has to be harvested from the patient, engineered and grown over several weeks, so treatment can start sooner. Talvey goes in as an injection under the skin, weekly or every other week after a step-up phase.
What the trial showed
AJMC reports that the 0.8 mg/kg dose produced an overall response rate of 73.6%, and the 0.4 mg/kg dose 73.0%. On the higher dose, 58% reached a very good partial response and the rate of complete response or better was 33%, with patients followed for a median of 6 months. For the lower dose the same two figures were 57% and 35%, after a median of 14 months of follow-up. About 85% of patients on the 0.8 mg/kg dose were still responding at 9 months or longer. The median length of response had not been reached on that dose, and stood at 9.5 months on the 0.4 mg/kg dose.
Ajai Chari, a University of California, San Francisco professor who directs its myeloma program, said the results were notable in heavily pretreated patients, some of whom had already had a BCMA-targeted bispecific or CAR-T therapy. “Patients at this stage of the disease have a poor prognosis,” he said.
The price of switching on T cells
Revving up the immune system carries risk. Cytokine release syndrome affected 79.0% of patients on the 0.4 mg/kg dose and 72.4% on the 0.8 mg/kg dose, though most cases were mild. Skin problems struck 55.9% and 67.6%, and 46.2% of the higher-dose group reported altered taste. Neurotoxicity, known as ICANS, occurred in 10% and 11%, mostly low-grade. Because of those dangers, the drug can be obtained only through a restricted safety program.
Europe moved on a different clock. A European Medicines Agency committee recommended conditional marketing authorization in July 2023, and as of BioSpace’s report in August the drug was still under review there.
Sources
- FDA Grants Talquetamab Accelerated Approval for R/R Multiple Myeloma (AJMC)
- TALVEY (talquetamab) (International Myeloma Foundation)
- Talvey Talquetamab Gets FDA Approval For Multiple Myeloma (BioSpace)
