Selinexor Triplet Shows Strong Clinical Activity in Relapsed/Refractory Myeloma

July 24, 2020
Hayley Virgil
Hayley Virgil

Senior Editor, OncLive®
Hayley Virgil heads OncLive's feature article efforts and specializes in social issues and equality in oncology. Prior to joining the company in early 2020, she worked as an editor in numerous industries, including media, marketing, hospitality, and computer science, and freelanced in subjects such as history, culture, and the natural sciences.

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.

References:

  1. Gasparetto C, Lentzsch S, Schiller GJ, et al. Selinexor, daratumumab, and dexamethasone in patients with relapsed/refractory multiple myeloma (MM). J Clin Oncol. 2020;38(suppl 15):8510. doi: 10.1200/JCO.2020.38.15_suppl.8510
  2. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455
  3. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551-1560. doi:10.1016/S0140-6736(15)01120-4

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