MM-403 Impact of Clonal Plasma Cells in Autografts on the Outcome of High-Risk Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplant

Context: Almost all patients with multiple myeloma (MM) undergoing an autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, and the risk is highest in patients with high-risk chromosomal abnormalities (HRMM). The significance of clonal plasma cells (CPC) in the autograft has not been clearly established. Objective: To determine the impact of CPC in the autograft on outcomes of patients with HRMM undergoing autoHCT. Methods: Adult patients with HRMM, defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by FISH, who underwent autoHCT between 2008-2018 and had 8-color next-generation flow cytometry (NGF) on the apheresis product for CPC were included, and divided into NGF+ or NGF- groups for CPC in the autograft. Results: 416 patients, 341 in the NGF- and 75 in the NGF+ groups, were included. Fewer patients in the NGF+ group achieved ≥VGPR after induction vs. the NGF- group (32% vs. 62%). Median follow up for the whole cohort was 35.7 (range 0.3-139.5) months. 100-day and best post autoHCT CR rates in the NGF+ and NGF- groups were 8% vs. 19% (p<0.001) and 33% vs. 54% (p<0.001), respectively. The NGF+ group also had lower rates of post-transplant MRD negativity (23% vs. 57%; p<0.001). Higher CPC number in the autograft was associated with inferior day 100 (p=0.017) and best post autoHCT (p=0.048) response rates. Median progression free survival (PFS) in the NGF+ vs. NGF- group was 12.8 vs. 32.1 months, respectively (p<0.001), and median overall survival (OS) was 36.4 vs. 81.2 months (p<0.001). In the subset of patients with ≥VGPR prior to transplant, those with NGF+ had inferior PFS (HR 3.38 [2.05-5.58], p<0.001) and OS (HR 2.29 [1.20-4.40], p=0.013) compared to the NGF- group. In multivariable analysis, the number of CPC in the autograft was predictive of worse PFS (HR 1.50 [1.12-1.99]; p=0.006), and worse OS (HR 1.35 [1.08-1.67]; p=0.007). Conclusions: Both the presence and the number of CPC in the autograft were highly predictive of post-transplant outcomes including PFS and OS in patients with HRMM. Novel strategies for ex-vivo purging of CPC could potentially improve patient outcomes.