P190 | ISATUXIMAB-CARFILZOMIB-DEXAMETHASONE AND AUTOLOGOUS STEM CELL TRANSPLANTATION: A PROMISING SALVAGE STRATEGY FOR YOUNG, FIT PATIENTS WITH FIRST-RELAPSE MULTIPLE MYELOMA.

Background: In the era of monoclonal antibodies, redefining salvage strategies for young, fit patients with relapsed multiple myeloma (MM) is critical. Isatuximab, carfilzomib, and dexamethasone (Isa-KD) have shown impressive efficacy. We explored the potential of Isa-KD integrated with a second autologous stem cell transplantation (ASCT) to establish a new intensive therapeutic platform in first-relapse MM. Methods: We retrospectively reviewed 5 young, fit patients treated at AOU Policlinico Federico II, Naples, Italy. All received frontline VTD induction, first ASCT, and lenalidomide maintenance (median 23 months, range 11–37). At first relapse, Isa-KD was initiated, bridging to a second ASCT. Patients exhibited varied risk profiles, including high-risk cytogenetics (gain 1q21, del(17p)). Results: All patients achieved deep responses post-salvage: 60% complete remission (CR), 40% very good partial response (VGPR). The median interval from Isa-KD start to ASCT was 6 months (range 4–8). After 24 months median follow-up, both median progression-free survival (PFS) and overall survival (OS) were not reached. One-year PFS and OS rates were 100%. Several patients (80%) experienced grade 2–3 thrombocytopenia, which occasionally required dose modifications and therapy delay. Despite these complications, treatment remained feasible overall: adverse events were manageable and did not lead to premature discontinuation. Infectious events were rare, and no treatment-related deaths occurred. Conclusions: The integration of Isa-KD with a second ASCT demonstrates unprecedented feasibility and efficacy, offering young, fit patients with first-relapse MM a potent, high-intensity treatment model. Our findings suggest a paradigm shift: leveraging immunotherapy with high-dose chemotherapy could optimize disease eradication early in the salvage setting. Prospective trials are urgently needed to validate this platform and define its role as a potential new standard of care for selected patients.