MM-329: Evaluation of Immunophenotype of the Non-Neoplastic Plasma Cell Compartment and Post-Therapy Immunomodulation to Understand Nuances in MRD Assessment of Multiple Myeloma Using Next-Generation Flow Cytometry

Abstract

Context A deeper understanding of the normal plasma cell (PC) compartment and changes in the immunophenotypic profile post-treatment is required to assess low levels of residual disease in multiple myeloma (MM) using multiparametric flow cytometry. Objective The expression profile of selective antigens on normal and aberrant plasma cells prior to and following anti-myeloma therapy was assessed to ascertain its relevance in MRD assessment. Design This is a prospective analysis of 702 patients with the diagnosis of MM (January 2015 to June 2020). Setting The study was conducted at a tertiary care cancer center. Patients A total of 702 cases (321 treatment naive; 321 post-therapy; 60 control samples) were evaluated. Sixty samples from non-MM staging marrow were assessed to study antigenic profiles of normal PC. Interventions Bone marrow samples were collected in EDTA and processed within 6 hours of collection per the consensus recommendation from the Euro-flow protocol using two tube 8-color/single tube 10-color panel. An aberrant PC cluster was defined by presence of >30 plasma cells with light chain restriction and/or aberrant immunophenotypes. Main Outcomes Measures 1. Expression profile of antigens on the polyclonal PC compartment; 2. Post-therapy immunomodulation in MM. Results Polyclonal PC were observed in 65.42% of treatment naive samples compared to 88.16% post-treatment samples (p=0.001). Frequency of aberrant expression of markers in polyclonal PC was higher at follow-up time point: CD45 (33% vs 38%; p=0.6), CD19 (19% vs 41%; p=0.001), CD56 (14% vs 41%; p Conclusions Flow cytometry-based MRD assessment in MM is challenged by wide immunophenotypic variation in non-neoplastic PCs and changes in immunophenotype after chemotherapy; thus, simultaneous analysis of multiple immunophenotypic markers, including light chain expression, is required for reliable MRD assessment.