Phase IIb Study Update: Selinexor Safely Augments Therapies for Refractory MM

For patients with multiple myeloma (MM) who experience disease relapse while receiving therapy with carfilzomib (CFZ), daratumumab (DARA), or pomalidomide (POM), a phase IIb study is in progress to investigate whether addition of selinexor to that therapy leads to improvement. A results update was presented in a poster session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, Illinois.

“Selinexor as an add-on to CFZ-, POM-, or DARA-based regimens, in patients actively progressing on these regimens, is well tolerated and safe. This trial demonstrates that selinexor can restore sensitivity to regimens to which MM patients are actively refractory,” wrote first author Noa Biran, MD, from the John Theurer Cancer Center at the Hackensack University Medical Center, Hackensack, New Jersey, and colleagues.

The study comprised three treatment arms, with a total cohort of 28 patients enrolled as of January 10, 2025. In each arm, selinexor was combined with CFZ, DARA, or POM therapy for MM; the patients enrolled in each arm had disease that had relapsed despite receipt of specific treatment. Patients in all three arms also received dexamethasone as part of the study combination.

Response to the particular combination therapy was evaluable in 24 patients. Seven of the patients withdrew consent, five because of disease progression. The 24 patients in the response-evaluable group had a median age of 68 years; 50% were men, and 54% were White. High-risk cytogenetics, including 1q21 duplication, t(4;14), and TP53 mutation, were found in 79% of these patients. Extramedullary disease was present in 21% of the patients, and 96% of the patients had a prior autologous transplant.

Over a median follow-up of 11.0 months, the response-evaluable group had an overall response rate of 38% and a clinical benefit rate of 83%. The median overall survival was not reached, and median progression-free survival was 5.7 months. The median treatment duration was 4.0 months, and median duration of response was 3.6 months.

In the response-evaluable group, the most common treatment-emergent adverse events (TEAEs) of grade 1 to 2 severity were electrolyte abnormalities and fatigue, reported by 50% and 38% of patients, respectively. The most common TEAEs of grade 3 or higher severity were neutropenia and pneumonia, reported by 25% and 8% of patients, respectively.

Three patients had treatment-related grade 3 serious adverse events: one had chest pain, which led to hospitalization; one had parainfluenza A-1 pneumonia, which led to a treatment delay; and one had sepsis plus pneumonia, which led to hospitalization and treatment interruption. All three patients recovered.

“Future studies can evaluate these combinations in the setting of chimeric antigen receptor T-cell bridging or in the post-bi-specific T-cell engager setting,” Biran and colleagues concluded.

The research presented at the Annual Meeting was funded by Karyopharm Therapeutics.