Graded Depth of Response and Neoplastic Plasma Cell Index as Indicators of Survival Outcomes in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant

Abstract

Abstract Objectives With a substantial number of patients with multiple myeloma (MM) experiencing disease relapse, the quest for more sensitive methods to assess deeper responses indicative of cure continues. Methods In this prospective analysis of 170 patients with MM at day 100 after autologous stem cell transplant, we evaluated the predictive value of conventional response, measurable residual disease (MRDTOTAL: the aberrant percentage of plasma cells [PC%] among total bone marrow cells), and neoplastic plasma cell index scores (NPCI: the aberrant PC% of total PCs). Results Significantly better progression-free survival (PFS) and overall survival (OS) were observed with deepening conventional response. Conventional response–based stratification within the MRD-positive and MRD-negative subgroups showed a significantly higher PFS (hazard ratio [HR], 3.11; P < .005) and OS (HR, 3.08; P = .01) in the conventional response-positive/MRD-positive group compared with the conventional response-negative/MRD-positive group. Using K-adaptive partitioning to find the optimum threshold for MRD, patients achieving less than 0.001% MRDTOTAL had superior PFS (MRDTOTAL 0.001% to <0.1%: HR, 6.66, P < .005; MRDTOTAL ≥0.1%: HR, 11.52, P < .005) and OS (MRDTOTAL 0.001% to <0.1%: HR, 5.3, P < .05; MRDTOTAL ≥0.1%: HR = 9.21, P < .005). The C index and Akaike information criterion metrics demonstrated the superior performance of the NPCI compared with MRDTOTAL in predicting treatment outcome. Conclusions Progressive deepening of response, conventional as well as MRD, correlates with superior survival outcomes. The NPCI proved to be a superior determinant of survival and can be explored as a better statistic than MRD.