The Food and Drug Administration has granted an accelerated approval to Xpovio in combination with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received more than four prior therapies.
The Food and Drug Administration (FDA) has granted an accelerated approval to Xpovio (selinexor) in combination with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received more than four prior therapies.
During its February meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 against an accelerated approval of the combination for the treatment of patients with penta-refractory multiple myeloma, expressing several concerns about the new drug application filed by Karyopharm — Xpovio’s manufacturer.
“With today’s accelerated approval of Xpovio by the FDA, patients with heavily pretreated multiple myeloma will now have a new therapeutic option to treat their disease,” said Dr. Sharon Shacham, founder, president and chief scientific officer of Karyopharm. “Discovering, developing and securing FDA approval for Xpovio with its novel mechanism of action over the past decade required the dedication of many people, including the patients, caregivers and physicians involved in our clinical trials, along with the many employees at Karyopharm. We are tremendously grateful for everyone’s contributions to this important milestone, and we look forward to the next stage in our pursuit of improving the lives of patients with cancer.”
First, the phase 2b STORM trial — a single-arm combination trial – and a prior phase 1 trial did not demonstrate strong single-agent activity with Xpovio. Therefore, isolating the specific impact of Xpovio appeared difficult. Additionally, there was significant toxicity with Xpovio in the STORM trial, including treatment-emergent side effects and serious side effects, as well as treatment-emergent side effects that resulted in patient deaths.
The panel members recommended the FDA wait for data from the phase 3 BOSTON trial so the agency to make a more informed decision on Xpovio. The open-label trial is evaluating the addition of Xpovio to Velcade (bortezomib) and low-dose dexamethasone versus Velcade and low-dose dexamethasone alone in patients with relapsed/refractory multiple myeloma who have received one to three prior regimens.
In the multicenter STORM trial, 122 patients with penta-refractory multiple myeloma were enrolled, 85 of whom were treated per-protocol. The average patient age was 65 years (ranging from age 40 to 85). Patients were treated with 80 mg of oral Xpovio plus 20 mg of oral dexamethasone twice weekly until disease progression. The primary endpoint was overall response rate and secondary endpoints included duration of response and clinical benefit rate.
To be eligible for enrollment, patients had to have received prior treatment with Velcade, Kyprolis (carfilzomib), Revlimid (lenalidomide), Pomalyst (pomalidomide), Darzalex (daratumumab), an alkylator and glucocorticoids. Those with smoldering multiple myeloma, plasma cell leukemia, systemic amyloid light chain amyloidosis and central nervous system myeloma were excluded.
In the study, patients had undergone an average of seven prior treatments and all were refractory to a proteasome inhibitor, immunomodulatory drugs, Darzalex or a glucocorticoid. Additionally, 96% of patients were refractory to Kyprolis, Pomalyst or Darzalex, 84% had undergone stem cell transplant and 28% had undergone two or more transplants.
The average time to response was one month and the average duration of response was 4.4 months. Response rates were similar, regardless of the patient’s last prior therapy.
The safety population included 123 patients from part two of the STORM trial. Treatment-emergent side effects occurring in over 20% of patients included anemia (65.9%), leukopenia (30.9%), neutropenia (38.2%), thrombocytopenia (71.5%), constipation (22%), diarrhea (42.3%), nausea (69.9%), vomiting (37.4%), fatigue (72.4%), weight decrease (48.8%), decreased appetite (53.7%), hyponatremia (35%) and dyspnea (21.1%).
Almost a third (28.5%) of patients discontinued study treatment due to a treatment-emergent side effect and 88.6% of patients needed one or more dose modification due to a treatment-emergent side effect. There were 23 patient deaths that occurred within 30 days of study treatment. Of these deaths, 10 were due to a fatal treatment-emergent side effect and 13 were due to disease progression.
Of the 23 deaths that occurred on or within 30 days of study treatment in part two of STORM, 13 (10.6%) were due to disease progression and 10 (8.1%) were due to a fatal treatment-emergent side effect.
“Despite recent advances in the treatment of multiple myeloma, almost all our patients will develop disease that is resistant to the five most commonly used anti-myeloma drugs we currently have available, and the prognosis for this patient population is particularly poor," said Dr. Paul Richardson, clinical program leader and director of clinical research of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute. "The accelerated approval of oral Xpovio marks an important advance in the treatment paradigm for patients with relapsed refractory multiple myeloma, and in my view, is an important addition to our therapeutic armamentarium."
This article was adapted from an article that originally appeared on OncLive as “FDA Approves Selinexor in Relapsed/Refractory Multiple Myeloma.”