Updated results from phase 2b study of selinexor in combination with carfilzomib, daratumumab, or pomalidomide in patients with multiple myeloma (MM) relapsing on current therapy.

7554 Background: Selinexor is a potent selective inhibitor of nuclear export and exhibits synergistic effects when combined with other myeloma therapies. Preliminary results on the combination of selinexor with carfilzomib (CFZ), daratumumab (DARA), or pomalidomide (POM)-based regimens in patients relapsing on therapy were reported (Biran 2023); overall response rate (ORR) Arm 1 (33%), Arm 2 (29%), and Arm 3 (44%). Herein we present the updated results with longer follow-up of selinexor plus CFZ, POM or DARA in MM patients relapsing on current treatment (NCT04661137). Methods: Patients were enrolled to each arm if their disease was refractory to the specific drug. Patients on Arm 1 were treated with selinexor 80 mg on D1, 8, 15; CFZ 20 mg/m 2 IV on D1, 8, 15; and dexamethasone (DEX) on D1, 8, 15, 22. Arm 2 patients received selinexor 60 mg on D1, 8, 15; POM 4 mg on D1-21; and DEX on D1, 8, 15, 22. Arm 3 patients were treated with selinexor 100 mg on D1, 8, 15, 22; DARA 16 mg/kg IV or 1,800 mg SQ on D1, 8, 15, 22 for C1-2; then D1 and 15 for C3-6; then D1 for ≥C7; and DEX on D1, 8, 15, 22. The primary objective was to investigate the ORR of selinexor plus CFZ, POM, or DARA-based regimens. Results: As of Jan 10, 2025, 28 patients were enrolled. Twenty-four were evaluable for response; 7 withdrew consent in which 5 were due to disease progression. Median age was 68 years (range 52-82), 50% male, 54% White, 96% had prior autologous transplant and 21% had extramedullary disease. Nineteen (79%) patients had high-risk cytogenetics, including 1q21 duplication (n=11), t(4;14) (n=8) and TP53 mutation (n=6). The ORR was 38% (95% CI, 19-59%) (PR, 8 [33%]) and clinical benefit rate (CBR) was 83% (95% CI, 63-95%) (PR, 8 [33%]; MR, 1 [4%]; SD, 11 [46%]). With a median follow-up of 11.0 months, the median PFS was 5.7 months (95% CI, 4.7-NR), and median OS was NR months (95% CI, 15-NR). Median DOR was 3.6 months (IQR, 2.5-5.1) with a median treatment duration of 4.0 months (range 0.3-10.8 mos). Most commonly reported Grade 1-2 TEAEs were electrolyte abnormalities (50%) and fatigue (38%). Most commonly reported grade ≥3 TEAEs were neutropenia (25%) and pneumonia (8%).Three patients experienced treatment-related grade 3 SAEs and recovered. One developed chest pain that required hospitalization. One had parainfluenza A-1 pneumonia requiring a treatment delay. One experienced sepsis and pneumonia which led to hospitalization and interruption of treatment. Conclusions: 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. 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. Clinical trial information: NCT04661137 .