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GPRC5D-Targeting Bispecific Antibody Talquetamab Promising in R/R Multiple Myeloma

December 10, 2022

Mid-January 2023

Leah Lawrence

Leah Lawrence is a freelance health writer and editor based in Delaware.

The bispecific antibody talquetamab elicited disease response in the majority of patients with heavily pretreated relapsed or refractory multiple myeloma (R/R MM), according to data from the phase I/II MonumenTAL-1 trial. In addition, these responses were quite rapid, explained Ajai Chari, MD, of the Icahn School of Medicine at Mount Sinai in New York, who presented the results at the 64th ASH Annual Meeting and Exposition.

“Patients’ median time to response was about 1.2 months, which is very encouraging,” Dr. Chari said. He noted the U.S. Food and Drug Administration has approved a variety of new immunotherapy treatment options for patients with MM in recent years, all of which target the B-cell maturation antigen (BCMA).

Talquetamab is a first-in-class, T-cell redirecting bispecific antibody that targets both G protein-coupled receptor family C group 5 member D (GPRC5D) and CD3 receptors.

Phase I studies of the drug established two recommended phase II doses: 0.405 mg/kg subcutaneous doses per week and 0.8 mg/kg subcutaneous doses every other week. The findings presented at the ASH meeting were from the dose-expansion cohorts that included 143 patients treated at the 0.4 mg/kg weekly dose and 145 patients treated with the 0.8 mg/kg dose every two weeks.

Patients included in the trial had a median of five prior lines of therapy over about 6.5 years, Dr. Chari said. Almost all patients were refractory to their last line of therapy, including about 70% who were triple-class refractory. Additionally, about one-third of patients had high-risk cytogenetics and about one-quarter had extramedullary disease (EMD).

The overall response rate in the two dosage groups was about 73%, Dr. Chari said. The response rate was maintained throughout various subgroups examined, with the exception of patients with EMD, including soft tissue plasmacytomas.

“EMD requires more investigation even in the era of T-cell redirection therapies,” Dr. Chari said.

In addition to being rapid, responses also appeared to be durable. Among patients who achieved complete remission or better, the median duration of response was not reached, a result that is outstanding, Dr. Chari said, given how heavily pretreated the patients were.

A separate cohort of 51 patients who had previously received therapies that redirect T cells also showed a 63% response to talquetamab.

Regarding safety, Dr. Chari said cytokine release syndrome (CRS) is a common adverse event seen with T-cell redirecting therapies. About 70% of patients treated with talquetamab experienced CRS, but it was primarily low-grade. There was a relatively low-to-modest rate of infections for such heavily treated patients compared to other therapies targeting BCMA. Grade 3-4 infections occurred in 17% of patients assigned to the 0.4 mg/kg dose and 11.7% of patients assigned to 0.8 mg/kg dose. There were two deaths from COVID-19. While rashes, taste changes, and nail disorders were common, they were typically low grade and clinically manageable so that patients could remain on treatment.

“I bring up these features because the lack of significant infection and toxicities seen with other myeloma agents (e.g., persistent cytopenias) means this drug could be readily combined with other agents,” Dr. Chari said.

Any conflicts of interest declared by the authors can be found in the original abstract.

Reference

Chari A, Touzeau C, Schinke C, et al. Talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): phase 1/2 results from MonumenTAL-1. Abstract #157. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 10, 2022; New Orleans, Louisiana.

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