<h3>Introduction</h3> Autologous stem cell transplantation (ASCT) is the standard-of-care for fit/younger patients with multiple myeloma. Outcomes are heterogeneous for those achieving less than a complete response (CR) after transplant; novel predictors of early relapse are needed to guide consolidation, maintenance and disease monitoring strategies. The post-ASCT proliferative index of clonal plasma cells (cPC) predicts for survival.<sup>1</sup> In the present study, we evaluated nonmalignant proliferating polyclonal plasma cells (pPC) for an independent effect on outcome. <h3>Methods</h3> From January 1 2013 to January 1 2014, 176 consecutive patients with multiple myeloma underwent their first ASCT at our institution and had a bone marrow (BM) specimen collected approximately 100 days post-ASCT. All BM was subject to multi-parametric flow cytometry using a BD FACS Canto II<sup>TM</sup> as previously described. Briefly, proliferating (S-phase) pPC were classified using DAPI staining and reported as a percentage of total pPC, which was calculated if there were at least 150 pPC/500000 events (Figure 1). Those with less than 150 pPC were deemed "non-evaluable." Time to next therapy (TNT) was calculated from ASCT Day 0 to the initiation of a new therapy (not including maintenance or consolidation), with patients censored at time of last follow-up or death without further therapy. Overall survival (OS) was calculated from Day 0 to death, with living patients censored at time of last follow-up. Statistics were performed using R 3.5.2. <h3>Results</h3> Responses at Day 100 were as follows: 71 (40%) CR, 48 (27%) very good partial response, 57 (33%) partial response or less. Among the 77 of 105 (73%) patients with <CR and at least 150 pPC, the median proliferating pPC percentage was 1.18% (interquartile range, 0.6-3.5%); 15 of 77 (20%) had ≥3% proliferating pPC. Proliferating pPC poorly correlated with proliferating cPC percentage (<i>R<sup>2</sup></i> = .006). When separating patients with ≥3% and <3% proliferating pPC, characteristics, e.g. high-risk cytogenetics, were balanced (Table 1). Patients with ≥3% proliferating pPC had significantly worse Day 100 responses and a trend toward worse best-responses post-ASCT (Table 1). TNT was significantly shorter in patients with ≥3% proliferating pPC (16.8 vs. 23.9 months, <i>p</i>= .0287); OS was comparable (Figure 2). In a multivariate Cox proportional hazard model adjusting for proliferating cPC (≥2% vs. <2%), proliferating pPC ≥3% remained a significant predictor for TNT (hazard ratio 2.80, 95% confidence interval 1.25-6.27, <i>p</i>= .0126). <h3>Conclusion</h3> Patients with multiple myeloma who failed to achieve CR by Day 100 post-ASCT with ≥3% proliferating pPC had significantly shorter TNT, independent of proliferating cPC. This is the first study to evaluate proliferating pPC as a prognostic marker, which could be a surrogate for a pro-proliferative BM microenvironment.