(PA-478) Selinexor in Combination with Pomalidomide and Dexamethasone for Patients with Relapsed and/or Refractory Multiple Myeloma (SCOPE Trial)

Background: Although outcome of patients (pts) with multiple myeloma (MM) has improved over the past decade, the cancer eventually relapses, and more treatment options are needed. Patients typically prefer oral and limited duration therapies. Selinexor is an oral, selective exportin 1 inhibitor, with established synergistic activity in combination with other anti-MM therapies.

Methods:

In this investigator-initiated, single arm, phase 2 trial, we evaluated the efficacy and safety of fixed-duration (18, 28-day cycles) comprising weekly selinexor (S), 60 mg orally (PO), pomalidomide (P), 4 mg PO, days 1-21 and dexamethasone (d), 40 mg PO, weekly in pts exposed to 1-2 prior lines of therapy, at least one of which included both a proteasome inhibitor (PI) and lenalidomide (IMiD).  Mandated anti-emetic prophylaxis included 5HT3 antagonist and olanzapine. The primary endpoint was overall response rate, based on confirmed response, with progression free survival (PFS), duration of response (DOR) overall survival (OS) and safety of SPd regimen being the key secondary endpoints.

 

Results:

Among 29 enrolled pts with relapsed/refractory (RR) MM, 28 were evaluable at data cutoff date (May 28, 2025); median follow-up for was 23.9 (range: 2.9-38.8) months. Median age at study entry was 67.5 (range: 65-72) years. 79% of pts received 2 prior lines of therapy, while in the remaining pts (21%), SPd was used as the first salvage regimen. All pts were exposed to a PI and IMiD (32% dual-refractory); 64% and 11% were daratumumab-exposed and refractory, respectively. Median number of cycles administered was 9 (range 1-18), with 36% of pts completing all 18 cycles of therapy. The overall response rate was 61% (95% CI:41-78), with 21% pts achieving measurable residual disease (MRD)-negative complete response (CR), 11% CR, 18% very good partial response (VGPR), 11% PR (partial response) as best response. minimal response and stable disease were noted in an additional 7% and 25%, respectively. Median PFS was 24 (95%CI 7.1-NE) months, and the median DOR was not reached (NR). OS at 2 and 3 years was 93% and 86.7% , respectively. 7% of patients discontinued SPd due to toxicity. No grade (Gd) 5 events or unexpected toxicities were observed during treatment. CTCAE v5 Gd 3+ hematologic toxicity occurred in 43% [Gd 3/4 anemia (11%/0%), thrombocytopenia (14%/0%), neutropenia (25%/7%), lymphopenia (4%/4%)] and Gd 3+ non-hematologic toxicity occurred in 46% [Gd ¾ (%); infections (21%/0%), fatigue (4%/0%), nausea (7%/0%), vomiting (0%/0%), diarrhea (0%/0%), anorexia (0%/7%) and weight loss (0%/0%]. Additional data will be presented at the meeting.

 

Conclusions:

Low dose selinexor in combination with Pd is an effective and safe regimen for pts with RRMM, previously exposed to a PI and an IMiD. An ongoing Phase 3 trial of SPd versus elotuzumab-Pd is expected to shed more light on this value of this combination.