Selinexor could be new ‘backbone’ in myeloma treatment
Selinexor and daratumumab in combination with dexamethasone was effective in patients with relapsed/refractory multiple myeloma, according to a presentation from ASCO20 Virtual Scientific Program.
Last year, the FDA approved the combination of selinexor (xpovio, Karyopharm Therapeutics) and dexamethasone for patients with heavily pretreated multiple myeloma.
“In the field of myeloma, selinexor is an inhibitor of exportin 1. It’s a very different mechanism of action from all the prior drugs that we have used in the treatment of myeloma,” Cristina Gasparetto, MD, associate professor of medicine at Duke University Medical Center, told Healio. “We wanted to determine if it could be a new backbone given in combination with other anti-myeloma agents.”
Gasparetto and colleagues determined the maximum tolerated dose and recommended phase 2 dose, as well as examined the safety, tolerability and efficacy of selinexor and dexamethasone combined with daratumumab (darzalex, Janssen) in patients with multiple myeloma refractory to proteasome inhibitors/immunomodulatory drug.
In this open-label, phase 1b/2 dose escalation and expansion study, researchers tested anti-CD38 monoclonal antibody-naive patients at the one dose level for each schedule: selinexor once-weekly (100 mg) or twice-weekly (60 mg) with dexamethasone 40 mg, and daratumumab 16 mg/kg IV was administered.
Investigators determined that 100 mg of selinexor weekly with dexamethasone 40 mg in combination with daratumumab as prescribed was the recommended phase 2 dose, Gasparetto told Healio.
Of the 34 patients in the study (twice-weekly group n = 3; once-weekly group n = 31), 62% were refractory to bortezomib and 65% were refractory to lenalidomide. The researchers reported an overall response rate of 73% (11 very good partial response and 11 partial response) for 30 daratumumab-naive patients and a clinical benefit rate of about 83%. In both groups, median progression free survival was 12.5 months, according to the abstract.
Gasparetto said they were able to manage toxicity when selinexor was given weekly. Common treatment related adverse events were thrombocytopenia, fatigue, nausea, anemia and neutropenia, according to the abstract. In the 60 mg twice-weekly cohort, two dose-limiting toxicities were reported (grade 3 thrombocytopenia and grade 2 fatigue), which required dose reduction in selinexor to 100 mg once-weekly; however, no dose-limiting toxicities occurred in the 100 mg once-weekly escalation cohort (n = 6).
“We concluded that this combination was effective. [This is] a solid new combination that can be offered to patients with prior exposure to [proteasome inhibitors] and [immunomodulatory drugs] and a new backbone in combination with daratumumab,” Gasparetto said.
Collapse
Gasparetto C, et al. Abstract 8510. Presented at: ASCO20 Virtual Scientific Program; May 28-31, 2020.
Read more about