First-in-Class Treatment Option for Resistant Myeloma
Testing a new first-in-class treatment option for patients with multiple myeloma refractory to most active available agents, a team led by Dan T. Vogl, MD, MSCE, of the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, found that selinexor in combination with low-dose dexamethasone produced an overall response rate of 21%. Dr. Vogl and colleagues reported their multicenter phase II trial results in the Journal of Clinical Oncology.
Selinexor, taken orally, inhibits selective exportin 1 (XPO1) and “induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs,” as explained by the authors.
In the study, 78 patients had received a median of 7 prior regimens. A total of 16 patients (21%), all with quad-refractory or penta-refractory disease, responded to the novel treatment (selinexor at 80 mg and dexamethasone at 20 mg twice weekly in 28-day cycles). Of the 78 patients, 17 had high-risk cytogenetics, including t(4;14), t(14;16), and del(17p); of them, 6 (35%) responded.
“The median duration of response was 5 months, and 65% of responding patients remained alive at 12 months,” noted the investigators. Adverse events led to dose interruption in 52% of patients, dose reduction in 37%, and treatment discontinuation in 18%. Selinexor (alone or in combination) is the focus of additional studies.