Prognostic value of minimal residual disease and polyclonal plasma cells in myeloma patients achieving a complete response to therapy

Achievement of a complete response has been associated with improved outcomes in patients with multiple myeloma. Recently, increasing application of minimal residual disease (MRD) assessment has shown that MRD negativity is a powerful prognostic factor for survival outcomes. We wanted to examine the impact of the polyclonal plasma cell (pPC) compartment among patients in complete response (CR) but are MRD positive. This is a retrospective cohort study where 460 myeloma patients were identified who met criteria for CR and had multicolor flow cytometry performed on the bone marrow (BM). Monoclonal and pPCs were estimated during MRD testing. Final outcomes including overall survival (OS) and time to next treatment (TTNT) were compared among the groups. The median OS for the entire cohort was not reached (95% CI; 63 mos, NR) and the median TTNT was 31 months (95% CI; 27,36). Among the MRD_neg group, median TTNT was 37.6 months vs 23 months for MRD_pos patients (P <.001); the median OS was not reached for either group, but there was a trend toward better survival for MRD_neg patients. Among the MRD_pos group, median percentage of pPCs was 65% (2.5–98.5), and those with >95% pPCs had a significantly better TTNT (NR vs 23 months; P =.02) and a trend toward better OS. We conclude that achievement of MRD negativity predicts for better response durability and trend toward improved OS and an increased proportion of pPC predicts for better outcomes within those who have residual tumor cells highlighting the importance of marrow normalization.