Results of the phase IIb STORM trial demonstrated that the combination of selinexor and dexamethasone demonstrated promising clinical activity in patients with penta-refractory multiple myeloma, a population that currently has no standard-of-care regimen.
Sundar Jagannath, MD
Results of the phase IIb STORM trial demonstrated that the combination of selinexor and dexamethasone demonstrated promising clinical activity in patients with penta-refractory multiple myeloma, a population that currently has no standard-of-care regimen.1
The data, which were presented at the 2018 SOHO Annual Meeting, showed that the doublet regimen was associated with an overall response rate (ORR) of 26.2% and a median overall survival (OS) of 8.6 months in patients with penta-refractory disease.
Sundar Jagannath, MD, director of the Multiple Myeloma Program and professor of medicine at The Tisch Cancer Institute, Mount Sinai Health System, delivered the STORM findings during the meeting. He added that patients who had a response to treatment, even a minor response, did significantly better with an OS of 15.6 months. Historically, the median OS in this patient population is an estimated 3.6 months.
“When patients relapse, it is a real challenge to manage,” he said. “There are no approved drugs established for this patient population.”
Investigators recruited 122 patients with penta-refractory multiple myeloma at 38 sites in the United States; 85 patients were treated per-protocol. The median patient age was 65 years (range, 40-85). Eligible patients had to have received prior treatment with bortezomib (Velcade), carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), daratumumab (Darzalex), an alkylator, and glucocorticoids.
Patients had undergone a median of 7 prior treatments (range, 3-18), and all were refractory to proteasome inhibitor/immunomodulatory drugs/ daratumumab/glucocorticoid. Ninety-six percent were refractory to carfilzomib/pomalidomide/daratumumab. Eighty-four percent had undergone stem cell transplant, and 28% had undergone ≥2 transplants.
Patients received 80 mg of oral selinexor plus 20 mg of oral dexamethasone twice weekly until progression. The primary endpoint was ORR.
Two patients, both of whom were negative for minimal residual disease, achieved stringent complete response. Two patients who relapsed following chimeric antigen receptor T-cell therapy achieved a partial response.
The median progression-free survival (PFS) was 3.7 months for the entire cohort. For partial responders, the median PFS was 5.3 months, and 4.6 months for those who had at least minimal response.
Duration of response was 4.4 months (range, <1-12.2). Jagannath said responses typically occurred in the first 4 weeks of treatment. The clinical benefit rate was 39.3% and the disease control rate was 78.7%.
“If you’re able to arrest the growth of the tumor, you’re able to get a survival benefit for these patients,” Jagannath said.
The most common grade 3/4 treatment-related hematological adverse event (AE) was thrombocytopenia (53.7%), followed by anemia (29.3%), neutropenia (17.9%), leukopenia (13.8%), and lymphopenia (8.9%). There was only 1 instance of grade 4 anemia and no grade 4 leukopenias recorded.
There were no grade 4 non-hematological AEs observed. The most common grade 3 non-hematological AEs were fatigue/asthenia (22.8%), hyponatremia (16.3%), and nausea (9.8%).
Selinexor links to and inhibits XPO1 (CRM1), a nuclear export protein. There is an accumulation of tumor suppressor proteins in the cell nucleus as a result of this activity, and, subsequently, the cell’s tumor suppressor function is regained and amplified, which investigators hypothesize induces apoptosis.
In previous results first presented at the 2016 ASH Annual Meeting and published this year in the Journal of Clinical Oncology, the selinexor/dexamethasone combination induced an ORR of 21% (95% CI, 13%-31%), with a response rate of 21% in patients with quad-refractory multiple myeloma (n = 48) and 20% in patients with penta-refractory disease (n = 30). In the overall population, the median PFS was 2.3 months and the median OS was 9.3 months.2,3