A triplet regimen comprised of selinexor, daratumumab, and dexamethasone proved to be highly active, inducing deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma.
A triplet regimen comprised of selinexor (Xpovio), daratumumab (Darzalex), and dexamethasone (SDd) proved to be highly active, inducing deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma, according to data from the phase 1b/2 STOMP trial (NCT02343042).1
Results from the trial presented during the 2020 ASCO Virtual Scientific Program revealed that the combination led to an overall response rate (ORR) of 69% in the overall patient population (n = 32), with a very good partial response (VGPR) rate of 34%, a partial response (PR) rate of 34%, and a clinical benefit rate (CBR) of 81%. The benefit with the triplet proved to be even more significant in daratumumab-naïve participants (n = 30). In this subgroup, the ORR was 73%, the VGPR rate was 37%, the PR rate was 37%, and the CBR was 87%. Moreover, the median progression-free survival with the selinexor regimen was 12.5 months.
“This combination appears to be highly active and produces a deep and durable responses in patients with relapsed/refractory multiple myeloma,” Cristina Gasparetto, MD, a professor of medicine and member of the Duke Cancer Institute said in a poster presentation during the meeting. “This supports further development of a novel non-proteasome inhibitor (PI, non-immunomodulatory (IMiD) backbone in early lines of therapy.”
Selinexor, a first-in-class oral selective XPO1 inhibitor, was approved by the FDA for use in combination with low-dose dexamethasone based on findings from the phase 2b STORM study, in which the agent induced an ORR of 26.2% with an overall duration of response (DOR) of 4.4 months in patients who were refractory to daratumumab, a PI, and an IMiD.2 When daratumumab was used as a single agent in patients with myeloma who were refractory to a PI and an IMiD, the agent yielded an ORR of 29% with a DOR of 7.4 months.3
In the multicenter, open-label, phase 1b/2 dose-escalation and expansion trial, the primary objective was to identify the maximum tolerated dose (MTD) of SDd, the recommended phase 2 dose (RP2D) of the combination, ORR, PFS, and DOR. To be eligible for enrollment, patients had to have received ≥3 previous lines of therapy for their disease, including a PI and an IMiD, or they had to have disease that was refractory to both a PI and an IMiD.
As of January 2, 2020, a total of 34 patients were enrolled in the trial; 3 patients received 60 mg of selinexor twice weekly plus once-weekly daratumumab at 16 mg/kg, while 31 received the RP2D of 100 mg of selinexor once weekly plus 16 mg/kg of daratumumab once weekly. The median age of participants was 68 years and 56% were male. The median number of prior treatment regimens received was 3.
“No dose-limiting toxicities were observed in the once-a-week administration,” noted Gasparetto. “Therefore the [recommended] phase 2 dose was established as [100 mg of selinexor] once weekly in combination with daratumumab and dexamethasone.”
With regard to safety, treatment-related adverse effects (AEs) occurred in ≥10% of the patients who received the RP2D. The most common hematological AEs reported with the regimen included thrombocytopenia (70.6%), anemia (61.8%), and neutropenia (50%). Gastrointestinal AEs such as nausea (70.6%), dysgeusia (41.2%), and anorexia (35.3%) were also reported, along with constitutional AEs, such as fatigue (61.8%), weight loss (23.5%), and dizziness (17.6%).
Among the total patient population, 9 patients experienced at least 1 serious AE (SAE); these events included rhinovirus infection (5.9%), thrombocytopenia (5.9%), pneumonia (5.9%), and acute kidney injury (2.9%), diarrhea (2.9%), fatigue (2.9%), hypokalemia (2.9%), infusion-related reaction (2.9%), nausea (2.9%), and vomiting (2.9%).
All non-homological AEs were categorized as grade 1 or 2 and were found to be reversable, regardless of supportive care. Meanwhile, hematological AEs were found to be manageable with dose interruptions or reductions, with or without supportive care.