Evaluation of MRD Status by Flow Cytometry and PCR in Multiple Myeloma Elderly Patients Receiving Autologous Stem Cell Transplantation After Bortezomib-Supplemented Mobilization and Conditioning

Abstract 4523 Autologous Stem Cell Transplantation (ASCT) is still an option for eligible patients with Multiple Myeloma (MM). High-dose melphalan (HDM: 200mg/m ∧ 2) is the recommended conditioning before ASCT, but synergistic effects of Bortezomib (BOR) and HDM have been reported in vitro and in vivo. PATIENTS AND METHODS: We evaluated in 56 MM fit elderly patients (median age 65 yrs), the feasibility and efficacy (also in terms of evaluation of minimal residual disease: MRD) of a strategy, combining BOR, Cyclophosfamide (CY) and dexamethasone (DEX) as induction and mobilizing therapy (CY-BOR), for ASCT, with conditioning including BOR-HD-MEL. The patients achieving at least PR after 4 CY-BOR courses, were mobilized with BOR and DEX standard schedule with CY 3g/m ∧ 2 (day 8). The pts collecting at least 2.5×10 ∧ 6CD34+/kg underwent ASCT with HD-MEL (day-1) and BOR (1.0mg/m ∧ 2 on -6,-3,+1,+4), followed by thalidomide consolidation until Relapse/Progression. The MRD has been prospectively evaluated both by using 4 colour flow cytometry (FC), and by using patient-specific probes, by ASO-PCR. The percentage of plasma cells (PCs) has been evaluated both in in PBSC harvested and in bone marrow, with CD38, CD45, CD56, CD138, CD19, CD27, CD28, CD117, kappa and lambda, along different steps of therapy. RESULTS: Of 44 pts evaluable for response before ASCT, 32 (73%) achieved 3 PR and 30 (68%) were mobilized: 29 (66%) collected 3 2.5×10 6 CD34+/kg and 25 underwent ASCT. Median time for PMN engraftment was 11 days (range 10–13) and 14 (range12–20) for PLT>=20.000/mcl. We observed grade 3 neuropathy in 3 patients and pneumonia during induction in 2 patients. At day +180 from ASCT 23 are evaluable for response and 21 for MRD: 3 pts have progressive disease (PD), 2 pts have a PR, 4 pts have a VGPR, 10 pts a nCR and 4 pts a CR. Four colour FC, in order to detect clonal plasmacells (cPCs) along several steps of treatment, showed that 3 pts (14%) achieved MRD negativity: 1/21 pts achieved MRD negativity at day +180 (cPC CONCLUSIONS: ASCT with HDM and BOR is feasible in older patients, with very high RRs and without major toxicities. We need a longer follow up and a larger number of pts to assess if these results will translate in a benefit in terms of outcome. Disclosures: Fragasso: Mundipharma: Honoraria.