P095 | Tumor burden and immune microenvironment influence response to anti-BCMA bispecific antibodies in relapsed/refractory multiple myeloma

Patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) face extremely poor outcomes, with median overall survival rarely exceeding 4–8 months despite intensive therapy. Against this dismal background, the advent of bispecific antibodies (BsAbs) has dramatically improved prognosis, producing deep and durable responses even in heavily pretreated individuals. Nevertheless, approximately 30–40% of patients exhibit primary resistance, underscoring the urgent need to identify predictive biomarkers of response to guide treatment selection and minimize unnecessary toxicity and cost.We conducted a retrospective study approved by the Ethics Committee of the University Hospital of Palermo to explore immunological and transcriptional determinants of response to new anti-MM BsAbs. In a cohort of 18 triple class exposed/refractory MM patients (7 treated with Teclistamab, 7 with Elranatamab, and 4 with Talquetamab), we integrated clinical, laboratory, and, where available single-cell RNA-seq/CITE-seq (SC) data to identify features associated with treatment resistance.Comparative analysis of 20 hematochemical parameters and 5 derived indices revealed that non responder patients presented an increased ISS stage (p=0.001), disease burden in term of monoclonal component (p=0.039), and a reduced Hemoglobin level (p:0.03). Interestingly, responders patients experienced a strong lymphocytes reduction between pre and post step-up dose (p