16 October 2023

Beneficial results have been seen during a trial a novel drug for treatment-resistant and refractory multiple myeloma.

In the phase 1/2 study, the drug mezigdomide is given orally alongside the steroid dexamethasone. The study has shown mezigdomide to have a “manageable safety profile and promising efficacy” for people with heavily pre-treated myeloma.

The research group, led by Dr Paul Richardson of Dana-Farber Cancer Institute, Boston, USA, explain that mezigdomide acts against tumours by modifying the action of a protein called cereblon E3 ubiquitin ligase.

This leads to the destruction of proteins called Ikaros and Aiolos. This is believed to cause cell death of multiple myeloma cells, and prevent them from proliferating, even in patients resistant to the drugs lenalidomide and pomalidomide.

In the phase 1 part of the study, the drug was given with dexamethasone to 77 patients with relapsed and refractory myeloma, to test its safety and determine a suitable dose for the next phase.

In the second phase, 1mg of mezigdomide per day was given to 101 patients for 21 days, then a week off, in each cycle. Adverse events were as expected, and mostly reversible.

The overall response rate was 41%, report the team in New England Journal of Medicine. Median progression-free survival was 4.4 months.

“The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects,” conclude the researchers.

Dr Richardson said: “We’re hopeful that this body of data provides substantial evidence of the value of this approach to patients with an urgent unmet medical need, and further supports this oral agent being tested in combination with other backbone therapies, where our preliminary results are already promising, and now are being evaluated as part of larger, ongoing phase 3 clinical trials.”

Source:

Richardson PG, Trudel S, Popat R, Mateos MV, Vangsted AJ, Ramasamy K, Martinez-Lopez J, Quach H, Orlowski RZ, Arnao M, Lonial S, Karanes C, Pawlyn C, Kim K, Oriol A, Berdeja JG, Rodríguez Otero P, Casas-Avilés I, Spirli A, Poon J, Li S, Gong J, Wong L, Lamba M, Pierce DW, Amatangelo M, Peluso T, Maciag P, Katz J, Pourdehnad M, Bahlis NJ; for the CC-92480-MM-001 Study Investigators. (2023) “Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma.” New England Journal of Medicine, doi: 10.1056/NEJMoa2303194

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2303194

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