10 January 2023

A novel treatment for relapsed multiple myeloma is showing good results in an international clinical trial, researchers have reported.

The experimental drug, talquetamab, is a bi-specific antibody therapy which redirects the immune system’s T cells to destroy myeloma cells expressing a protein made by the GPRC5D gene.

It was tested in the MonumenTAL-1 Phase 1/2 study by a team led by Dr Ajai Chari of the Mount Sinai Hospital in New York, USA.

In the phase 1 study, the team recruited 232 patients with heavily pre-treated relapsed or refractory multiple myeloma. The drug was given intravenously or subcutaneously at various doses, either weekly or fortnightly.

In the first group, patients received talquetamab subcutaneously at 405µg per kilogram body weight, weekly, and 70% of patients responded. In the second group, who received 800µg per kg every two weeks, 64% of the patients responded. These responses lasted a median of ten and eight months, respectively.

In the New England Journal of Medicine, the researchers report on side-effects from the phase 1 study. Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment, but were mostly mild. Very few patients (5 to 6%) stopped talquetamab treatment because of side effects, the researchers say.

The researchers conclude: “Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma.”

Dr Chari said: “This means that almost three-quarters of these patients are looking at a new lease on life.

“Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients.”

Results of the phase 2 trial, validating the findings of the phase 1 study, were reported at the American Society of Hematology annual meeting on 10th December 2022.

Source:

Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodríguez-Otero P, Askari E, Mateos MV, Costa LJ, Caers J, Verona R, Girgis S, Yang S, Goldsmith RB, Yao X, Pillarisetti K, Hilder BW, Russell J, Goldberg JD, Krishnan A. (2022) “Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.” New England Journal of Medicine, doi:

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10.1056/NEJMoa2204591

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2204591

https://ash.confex.com/ash/2022/webprogram/Paper159707.html