Aponermin-based regimen as bridging therapy prior to CAR-T cell therapy for relapsed/refractory multiple myeloma

Abstract Object To observe the efficacy and safety of Aponermin-based regimen utilized as bridging therapy before CAR-T cell therapy in patients with relapsed/refractory multiple myeloma, and to assess its impact on the subsequent CAR-T cell therapy. Methods A 48-year-old male was diagnosed with multiple myeloma (IgA-λ type, R-ISS Stage III, with extramedullary involvement) in December 2022. He received induction therapy with the PAD regimen (bortezomib, liposomal doxorubicin, dexamethasone) and DKd regimen (daratumumab, carfilzomib, dexamethasone), achieving a Very Good Partial Response (VGPR). Subsequently, he underwent tandem autologous peripheral blood hematopoietic stem cell transplantation. Maintenance therapy with the KP regimen (carfilzomib, pomalidomide) was administered, during which surveillance studies showed minimal residual disease (MRD) negativity by bone marrow flow cytometry and negative serum and urine immunofixation electrophoresis. However, 11 months post-transplant, the disease relapsed, evidenced by MRD conversion to positive on bone marrow flow cytometry and seroconversion on serum immunofixation electrophoresis. CAR-T cell therapy was planned. Lymphocytes were collected via apheresis on February 22, 2025, for CAR-T cell manufacturing. Bridging therapy was initiated the following day (February 23, 2025) with Aponermin (10mg/kg on Days 1-5), Selinexor (40mg once weekly), and dexamethasone (20mg once weekly). CAR-T cell therapy with Zevorcabtagene autoleucel (zevor-cel) at a dose of 1.5 × 10^8 CAR-T cells was administered on March 31, 2025. Results After one cycle of the Aponermin-containing regimen, bone marrow flow cytometry showed conversion of minimal residual disease (MRD) from positive to negative. During CAR-T cell therapy, the patient experienced only Grade 1 cytokine release syndrome (CRS), manifesting solely as fever, which resolved with symptomatic management using non-steroidal anti-inflammatory drugs (NSAIDs). No requirement for red blood cell or platelet transfusions post-CAR-T infusion, and no infectious complications occurred. At the last follow-up on May 31, 2025, evaluations demonstrated negative serum and urine immunofixation electrophoresis, and sustained MRD negativity by bone marrow flow cytometry. Conclusion This case report describes the role of Aponermin-based regimen as bridging therapy prior to CAR-T cell therapy, demonstrating favorable efficacy without compromising subsequent CAR-T cell treatment. The regimen did not adversely impact hematologic recovery following CAR-T cell infusion, and cytokine release syndrome (CRS) was mild and manageable. For patients with triple-class refractory (TCR) or penta-drug refractory multiple myeloma undergoing CAR-T cell therapy, Aponermin-based regimen represents a viable and well-tolerated bridging option with a manageable safety profile.