30 August 2019

US doctors have reported promising results from a trial of selinexor as a treatment for multiple myeloma.

The drug combination selinexor plus dexamethasone appears to be helpful for patients whose disease have not responded well to several therapies.

Dr Sundar Jagannath of Mount Sinai Health System, New York, USA, and colleagues report that this combination significantly knocked down the cancer in over a quarter of patients, with two patients going into complete remission.

Selinexor is an inhibitor of nuclear export protein XPO1. The drug blocks the transfer of protein and messenger RNA from the nucleus of the cancer cell to the cytoplasm, leading to the death of the cell.

The phase 2b trial, called STORM Part 2, involved 122 patients across the US and Europe who had been previously treated with drugs from three different classes – so called ‘triple-class refractory’. The results were published in the New England Journal of Medicine.

On treatment with selinexor and dexamethasone, 26% of patients had a partial response or better, with two patients going into complete remission. At least a minimal response was seen in almost 40% of multiple myeloma patients within one or two months. The median progression-free survival was 3.7 months, and median overall survival was 8.6 months.

Side effects included low blood count without bleeding, nausea, vomiting, lack of appetite, and fatigue.

Dr Jagannath said: “This study proved that a novel, first-in-class drug with a new mechanism of action can kill a patient's cancer cells. This proved that the drug worked in patients who had exhausted every other treatment and who would have been placed on hospice care otherwise.”

Co-author Dr Ajai Chari added: “This study is meaningful for patients with multiple myeloma who haven't had success on multiple other therapies.

“An increasing number of patients have resistance to the standard drugs used in the treatment of multiple myeloma, and the overall survival in these patients is short, sometimes less than three months.”

Source: Chari, A., Vogl, D.T., Gavriatopoulou, M., Nooka, A.K., Yee, A.J., Huff, C.A., Moreau, P., Dingli, D., Cole, C., Lonial, S., Dimopoulos, M., Stewart, A.K., Richter, J., Vij, R., Tuchman, S., Raab, M.S., Weisel, K.C., Delforge, M., Cornell, R.F., Kaminetzky, D., Hoffman, J.E., Costa, L.J., Parker, T.L., Levy, M., Schreder, M., Meuleman, N., Frenzel, L., Mohty, M., Choquet, S., Schiller, G., Comenzo, R.L., Engelhardt, M., Illmer, T., Vlummens, P., Doyen, C., Facon, T., Karlin, L., Perrot, A., Podar, K., Kauffman, M.G., Shacham, S., Li, L., Tang, S., Picklesimer, C., Saint-Martin, J.R., Crochiere, M., Chang, H., Parekh, S., Landesman, Y., Shah, J., Richardson, P.G., Jagannath, S. (2019) “Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma”, N Engl J Med, available from doi: 10.1056/NEJMoa1903455


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