Bispecific antibodies are synthetic proteins that are capable of binding to 2 different sites, either on the same cell or separate ones. They are frequently used in relapsed or refractory multiple myeloma to help T cells bind to cancer cells. Talquetamab is a bispecific antibody that targets CD3 receptors on T cells as well as GPRC5D receptors on malignant plasma cells. A study recently published in the New England Journal of Medicine evaluated the dose-limiting toxic effects, adverse events, and laboratory abnormalities associated with subcutaneous administration of talquetamab.
For this study, talquetamab was given in several different subcutaneous dosages to determine the recommended doses for a phase II study. At the cutoff date, 2 target doses were identified for inclusion in phase II: 405 μg/kg weekly (30 patients) and 800 μg/kg every other week (44 patients).
In the 74 patients who received these doses in phase I, common adverse events were cytokine release syndrome, skin-related events, and dysgeusia. The breakdown is as follows:
- 405 μg/kg weekly (30 patients)
- 77% experienced cytokine release syndrome
- 67% experienced skin-related events
- 63% experienced dysgeusia
- 800 μg/kg every other week (44 patients)
- 80% experienced cytokine release syndrome
- 70% experienced skin-related events
- 57% experienced dysgeusia
Despite the frequency of adverse events, most were mild, with only 1 patient experiencing grade 3 rash in the 800 μg/kg every other week group. For those in either group experiencing cytokine release syndrome, only 1 patient had higher than a grade 1/2 event.
Response rates were good in both groups, with 70% achieving response at 11.7 months median follow-up for those receiving 405 μg/kg weekly and 64% achieving response at 4.2 months median follow-up for those receiving 800 μg/kg every other week.
“Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma,” the authors concluded. “Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade.”
Reference
Talquetamab, a T-cell–redirecting GPRC5D bispecific antibody for multiple myeloma
