Real-world safety and efficacy of aponermin and selinexor-based regimens in patients with multiple myeloma Free

Background: Treatment of relapsed/refractory multiple myeloma (RRMM) and frail newly diagnosed multiple myeloma (NDMM) patients remains challenging despite therapeutic advances. Aponermin (Apo), a novel recombinant circular TRAIL protein that induces selective apoptosis in tumor cells, and selinexor, a first-in-class selective inhibitor of nuclear export (SINE), represent innovative approaches for MM treatment (Dhillon S, Drugs, 2024; Jun Ma, Leukemia & Lymphoma, 2024). This study evaluated the real-world safety and efficacy of aponermin combined with selinexor-based regimens in MM patients.

Methods: We retrospectively analyzed clinical data from 26 MM patients treated with aponermin and selinexor-based regimens, of whom 92.31% had RRMM and 7.69% had newly diagnosed MM (NDMM). The primary endpoints included overall response rate (ORR), duration of response (DOR), and adverse events.

Results: The median age was 66 years (range 29-82), with 65.38% male patients. R-ISS staging showed 11.54% stage I, 42.31% stage II, and 30.77% stage III. High-risk cytogenetic abnormalities included 1q21 gain/amplification (50.00%), t(4;14) (19.23%), 17p deletion (15.38%) and double-hit HRCA (26.92%). Extramedullary disease was present in 26.92% of patients (19.23% paraosseous, 7.69% extraosseous). Patients received a median of 2 prior lines of therapy (range 0-9), with 57.69% previously exposed to proteasome inhibitors, immunomodulatory drugs and CD38 monoclonal antibody combinations. Treatment regimens predominantly consisted of Apo+selinexor+dexamethasone (65.38%), with other combinations including Apo + daratumumab + selinexor + dexamethasone (11.54%), Apo + selinexor + carfilzomib + pomalidomide + dexamethasone (7.69%), Apo + selinexor + pomalidomide + dexamethasone (7.69%), Apo + selinexor + carfilzomib + dexamethasone (3.85%) and Apo + selinexor + cyclophosphamide + dexamethasone (3.85%). The median number of treatment cycles was 3 (range 2-8). The ORR was 61.54%, including complete response (15.38%), very good partial response (19.23%), and partial response (26.92%). Additionally, 11.54% achieved minimal response and 26.92% stable disease, with no progressive disease observed during initial assessment. The median DOR was 3.3 months (range 1.0-6.4). The safety profile was manageable, with the most common adverse events being leukopenia (15.38%), thrombocytopenia (15.38%), and liver function abnormalities (15.38%). Other adverse events included anemia (7.69%), nausea/vomiting (7.69%), constipation (3.85%), dizziness (3.85%), palpitations (3.85%), and fever (3.85%).

Discussion: This real-world analysis demonstrates that aponermin combined with selinexor-based regimens provides promising efficacy with a manageable safety profile in heavily pretreated RRMM patients. The high response rate suggest this novel combination may offer a valuable treatment option for this challenging population, warranting further investigation in larger prospective studies.