P-341: Response and Safety of Selinexor with VRD Regimen in Newly Diagnosed Multiple Myeloma (NDMM) with Extramedullary Disease (EMD): A Prospective, Open-Label, Multicenter, Phase 2 Study

Introduction: Extramedullary disease (EMD) is rare in newly diagnosed multiple myeloma (NDMM) patients, associated with poorer prognosis and drug resistance. In this context, we present the preliminary findings from a prospective phase 2 study evaluating the safety and efficacy of selinexor in combination with VRd as a first-line treatment for NDMM patients with EMD(NCT05900882).

Methods: The study enrolled NDMM patients under 75 years old who exhibited measurable extramedullary disease. Pts received selinexor (60 mg QW) in combination with VRd (SVRD) regimen as induction therapy for 4 cycles (28 days of each cycle). Following the induction phase, pts underwent two cycles of VRd consolidation therapy after autologous stem cell transplantation (ASCT), while those who did not undergo ASCT received another 4 cycles of SVRD consolidation therapy. All pts received bortezomib plus lenalidomide for maintenance for at least 24 months. The primary endpoint of the study was the best response rate during induction therapy, and secondary endpoints included complete response (CR) rate, duration of response (DOR), safety, and survival outcomes.

Results: Between Oct 17, 2022 and May 17, 2024, a total of 19 NDMM pts with EMD were enrolled and received treatment. The median age was 58 years (range 43-70). Among them, 14 patients (73.7%) had ISS stage II/III disease. FISH was not available in 4 patients. 8 patients of the remaining 15 patients (53.3%) were classified as high risk based on the mSMART stratification, 5 patients(33.3%) was double-hit. 18 patients (94.8%) had EM-B(extramedullary bone-related plasmacytoma). 5 patients (26.3%) had EM-S (soft tissue-related plasmacytoma). 4 patients (21%) had both EM-B and EM-S. By the data cut-off, at a median treatment time of 12 months (range 0.3-19 months), 13 pts completed 4 cycles of SVRd inductive treatment, 7 pts underwent ASCT, 2 pts underwent CART, 2 pts had progressive disease during induction therapy. 1 pts had progressive disease after ASCT.

Among the 19 evaluable pts for best serological response, 5 pts (26.3%)achieved serological CR/sCR, and 7 pts (36.8%) achieved VGPR. The depth of remission improved with the continuous treatment. Continuous extramedullary disease evaluation in 15 patients showed complete disappearance of extramedullary lesions in 8 patients (53.3%), PR in 6 patients (40%), and SD in 1 patient (6.6%). 14 (73.6%) pts experienced any grade AE. Grade 3 or 4 AEs were reported in 5 pts (6 events in total), with the most common being thrombocytopenia (4/19). Non-hematological AEs were mainly grade 1-2. 3 pts were required dose reductions to 40 mg.

Conclusions: The combination of selinexor with VRd regimen demonstrated early, deep, and durable responses in NDMM patients with extramedullary disease, both in serological and extramedullary responses, with a manageable safety profile.