A substantial proportion of patients with heavily pretreated multiple myeloma (MM) responded to treatment with the bispecific antibody talquetamab, according to results of a phase I study published in The New England Journal of Medicine.
Talquetamab is a bispecific antibody that binds to CD3 receptor on T cells and G protein-coupled receptor, family C, group 5, member D (GPRC5D). GPRC5D is an orphan receptor expressed primarily in plasma cells, hair follicles of the skin, and hard keratinized tissues. In this early study, talquetamab yielded a response in 64% to 70% of patients, depending on the dose level, with a side effect profile that was mostly grade 1 or 2 and managed with supportive care.
According to researchers led by Ajai Chari, MD, of Mount Sinai School of Medicine in New York, “talquetamab can be readily available off the shelf with convenient subcutaneous administration so that potential delays, attrition, and the burden associated with generating patient-specific CAR [chimeric antigen receptor] T-cell therapy can be avoided.”
Following the publication of these results, and simultaneous presentation at the 64th American Society of Hematology Annual Meeting and Exposition, talquetamab’s manufacturer submitted a biologics license application to the U.S. Food and Drug Administration for the treatment of relapsed or refractory MM. If approved, it would join teclistamab as an available bispecific T-cell engaging antibody for this patient population.
In the study, 232 patients received talquetamab intravenously weekly or every other week in doses from 0.5 to 180 μg/kg (n=102) or subcutaneously weekly, every other week, or monthly from 5 to 1,600 μg/kg (n=130).
Patients were heavily pre-treated with a median of six lines of therapy, and all had progressed on or been intolerant of prior approved therapies.
Based on these results, Dr. Chari and colleagues recommended two subcutaneous doses for phase II evaluation: 405 μg/kg weekly (n=30) and 800 μg/kg every other week (n=44).
Among patients assigned to 405 μg/kg/week, the median follow-up was 11.7 months. Seventy percent of these patients responded to treatment (95% CI 51-85), and the median duration of response was 10.2 months.
Median follow-up was 4.2 months at the 800 μg/kg dose, and 64% of these patients responded to treatment (95% CI 48-78). Median duration of response was 7.8 months.
Looking at specific subgroups, Dr. Chari and colleagues found that 65% and 70% of patients with triple-class refractory disease responded at the 405 μg and 800 μg dose levels, respectively. Among 16 patients with previous T-cell redirecting therapies targeting B-cell maturation antigen, 50% responded, suggesting “that an effective immune response can be mounted against a different antigen even after previous exposure and disease progression with T-cell therapy,” the researchers wrote.
The majority of patients at both dose levels experienced cytokine release syndrome (CRS; 77% and 80%); all but one were grade 1 or 2. The events occurred primarily during step-up dosing and after the first full dose of the drug. All CRS events that occurred after the first full dose were grade 1. Treatment-related neurologic events were documented in 10% of patients at the 405 μg dose level, all of which were grade 1 and 2.
Most patients also experienced skin-related events (67% and 70%) and dysgeusia (63% and 57%). At 800 μg/kg there was one dose-limiting toxicity of grade 3 rash; this side effect was not totally unexpected given the known expression patterns of GPRC5D. Infections were also common, noted in 47% of patients treated at the 405 μg dose level.
Dr. Chari and colleagues noted that the results are limited by the early and ongoing status of the study, which included only a small number of patients at each dose, and its single-group design. Direct comparison to other available MM treatments is not currently available.
The study was supported by Janssen Research and Development. Any conflicts of interest declared by the authors can be found in the original article.
Leah Lawrence is a freelance health writer and editor based in Delaware.
Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244.