TOPLINE:

In newly diagnosed patients with multiple myeloma (MM), adding selinexor (Xpovio) to lenalidomide (Revlimid) maintenance therapy after autologous stem-cell transplant (ASCT) did not improve progression-free survival (PFS) but led to notable increases in serious adverse events, according to research presented at the American Society of Hematology (ASH) 2025 Annual Meeting.

METHODOLOGY:

• Can adding more drugs to lenalidomide maintenance improve outcomes? Researchers aimed to answer that question with the addition of selinexor, a first-in-class, oral selective inhibitor of nuclear exportin 1.
• In the phase 3 randomized ALLG MM23 SeaLAND trial, researchers enrolled 149 patients with newly diagnosed MM who had undergone ASCT between 2020 and 2024.
• Patients (mean age, 62) had received three to six cycles of bortezomib- or lenalidomide-based induction, undergone ASCT, and had an Eastern Cooperative Oncology Group Performance Status score of 0-2.
• Between 75 and 115 days post-ASCT, patients were randomized 1:1 to low-dose selinexor (40 mg weekly) with lenalidomide (10 mg on days 1-21, n = 84) or lenalidomide-alone (n = 65) in a 28-day cycle.
• The mean number of completed cycles was 17 for lenalidomide alone vs 15 for selinexor-lenalidomide (P = .25). Median follow-up was 24 months for the lenalidomide alone group and 25 months for the selinexor arm.

TAKEAWAY:

• Adding selinexor to lenalidomide maintenance did not improve PFS compared to lenalidomide alone. At 30 months, the PFS rates were similar between the two groups: 65% for selinexor-lenalidomide and 69% for lenalidomide alone (hazard ratio, 1.13; P = .71).
• Rates of grade 3 or higher events were much more common in the selinexor-lenalidomide group. Patients receiving selinexor vs lenalidomide alone had higher rates of febrile neutropenia (10% vs 0%), upper respiratory infections (9% vs 0%), neutropenia (61% vs 33%), thrombocytopenia (26% vs 2%), as well as fatigue and nausea (8% vs 0%).
• The most common adverse events of any grade were also more common in the selinexor-lenalidomide arm.
• Patient-reported outcomes, which included global health status and health-related quality-of-life scores, remained similar between both treatment arms throughout the study.

IN PRACTICE:

“Although a negative study, these results are important and suggest that due to toxicity, selinexor may be better suited to induction rather than maintenance,” the authors wrote.

Medscape Medical News contributor Manni Mohyuddin, MD, assistant professor in the MM program at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, had another take.

“This trial should be a nail in the coffin for routine usage of this drug,” Mohyuddin wrote in perspective on ASH 2025 research. “A broader question, although difficult to answer, is whether precious taxpayer money should have funded this trial, or whether it should have been done by industry alone.”

LIMITATIONS:

Treatment was discontinued for reasons other than study closure in 43 patients in the selinexor-lenalidomide group and 20 patients in the lenalidomide-alone group.

DISCLOSURES:

Multiple authors reported various relationships with pharmaceutical companies.