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

Abstract

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. To determine the impact of CPC in the autograft on outcomes of patients with HRMM undergoing autoHCT. 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. 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). 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.