P143 | PROSPECTIVE EVALUATION OF THE IMPACT OF DARATUMUMAB-CONTAINING INDUCTION REGIMENS ON STEM CELL MOBILIZATION, COLLECTION AND ENGRAFTMENT IN TRANSPLANT ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: RESULTS OF AN ITALIAN MONOCENTRIC EXPERIENCE

In recent years, with the wide use of anti-CD38 monoclonal antibody Daratumumab (DRT) in newly diagnosed multiple myeloma (NDMM), concerns emerged regarding potential negative effects following DRT on stem cell mobilization and bone marrow engraftment. We conducted a prospective study at Fondazione Policlinico A. Gemelli IRCCS, including NDMM patients consecutively treated with DRT-based induction regimens for the years 2022-2024. The primary outcome was the completion at first apheresis of a target cell dose ≥ 4x10^6 CD34+ cells/Kg (EBMT guidelines for tandem ASCT). Secondary outcomes were the median dose of CD34+ cells/kg collected at first apheresis, plerixafor need, the rate of mobilization failures, engraftment time, and transfusion requirements after ASCT. The study was registered online at http://clinicaltrials.gov with the identifier NCT05835726. Sixty-six patients (median age 60 yo, M/F 44/22) were prospectively enrolled and compared with 84 controls treated in our division before the introduction of DRT (2019-2021). The two groups were comparable for demographics and disease-related variables, whereas DRT-receiving patients were mobilized with an inferior dose of cyclophosphamide (CTX). In comparison with controls, patients in the prospective group had a lower PB CD34+ cell concentration on the day before apheresis (25/μL and 37/μL, median values in patients and controls, respectively, p<0.001), at apheresis (53/μL and 117/ μL, p<0.001), and collected less CD34+ cells (3.7 and 6.6 x10^6/kg, p<0.001). In addition, 21 DRT-receiving patients (31.8%) and 7 (8.3%) controls received plerixafor (p<0.001) (Table 1. A). After matching the patients through a propensity score by the CTX dose, 44 patients per group were identified. In comparison with controls, DRT-receiving patients showed significantly lower stem cell yields (3.8 and 6.3×10^6/kg, p=0.029), and more frequently needed plerixafor (27.3% and 9.1%, p=0.027) (Table 1.B). In total, 41 patients in the DRT group and 39 controls underwent one ASCT, while 19 and 37 underwent two ASCTs. The two groups received a comparable CD34+ cell content in infused grafts and displayed similar neutrophil and platelet engraftment after the first and second ASCT, while DRT-receiving patients experienced higher platelet transfusion needs at the first ASCT (p=0.036). Our data suggests that DRT may impair stem cell mobilization. Higher CTX doses and Plerixafor rescue are feasible strategies to mitigate the DRT effects.