Medically reviewed by Dr. Shani S. Saks, D.O. on August 2, 2023
In a phase 1 study, talquetamab induced a substantial therapeutic response in patients suffering from multiple myeloma. The bispecific antibody was safe except for low-grade cytokine release syndrome, dysgeusia, and skin-related events.
Malignant plasma cells in multiple myeloma express the G protein-coupled receptor, family C, group 5, member D (GPRC5D), an orphan receptor. Talquetamab is a bispecific antibody directed against GPRC5D, which leads to the redirection of T cells to kill myeloma cells that express GPRC5D.
This study, published in The New England Journal of Medicine, evaluated the safety and efficacy of talquetamab in patients with refractory or relapsed multiple myeloma.
A total of 232 patients were enrolled in this study, with subcutaneous talquetamab administration in 130 patients and intravenous talquetamab administration in 102 patients. Discontinuation of treatment occurred in 164 patients, which was commonly due to progressive disease. The median age of the patients in the subcutaneous talquetamab and intravenous talquetamab groups was 64 (39–84) years and 65 (33–79) years, respectively.
Safety of Talquetamab in Multiple Myeloma Patients
In the dose-escalation phase, dose-limiting toxic effects were observed in four patients. Grade 3 or 4 adverse events were observed in 87%, 86%, and 90.2% of patients in the subcutaneous talquetamab 405 µg, subcutaneous talquetamab 800 µg, and intravenous talquetamab groups, respectively.
Common adverse events included low-grade cytokine release syndrome, dysgeusia, and skin-related events. All patients experiencing cytokine release syndrome were offered supportive treatment. The most common grade 3 or 4 adverse events comprised hematologic toxic effects. Serious adverse events in the form of single events occurred in 34% of the 800 µg dose group, 43% of the subcutaneous talquetamab 405 µg group, and 34% of patients in the intravenous talquetamab group.
Efficacy of Talquetamab in Multiple Myeloma Patients
In the subcutaneous talquetamab 405 µg group, 70% of the patients had a response that could be evaluated, with 23% of these patients showing a complete or better response. In the subcutaneous talquetamab 800 µg group, 64% of the patients had an evaluable response. Approximately 72% of the patients had an evaluable response in the intravenous talquetamab group.
The median time to response to talquetamab in the subcutaneous talquetamab 405 µg and subcutaneous talquetamab 800 µg groups was 0.9 and 1.2 months, respectively. Substantial treatment response with subcutaneous treatment was reported in patients with triple-class-refractory and penta-drug-refractory disease.
Chari, A., Minnema, M. C., Berdeja, J. G., Oriol, A., van de Donk, N. W. C. J., Rodríguez-Otero, P., Askari, E., Mateos, M.-V., Costa, L. J., Caers, J., Verona, R., Girgis, S., Yang, S., Goldsmith, R. B., Yao, X., Pillarisetti, K., Hilder, B. W., Russell, J., Goldberg, J. D., & Krishnan, A. (2022). Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. New England Journal of Medicine, 387(24), 2232–2244. https://doi.org/10.1056/nejmoa2204591