Pb2072: circulating cd71+ myeloid precursors in mgus and multiple myeloma: a prospective survey

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Our previous work showed that impaired maturation of neutrophils is implied in the progression from monoclonal gammopathy of undetermined significance (MGUS) through Multiple Myeloma (MM). Hematopoietic stem and progenitor cells (HSPCs) are variously involved in the primary immune response to various pathological conditions, serving as a link with the accumulation of myeloid-derived suppressor cells (MDSCs). Recently, the first progenitors of neutrophils have been found in peripheral blood, arising from the expression of CD71 as a marker associated with the early stages of neutrophil proliferation (Lin-CD66b+CD117+CD71+) [Dinh et al. – Immunity 2020]. These findings could potentially play an important biological and clinical role in identifying MM patients with worse outcomes. Aims: Measurement of myeloid precursors in the peripheral blood of patients with plasma cell dyscrasias by flow cytometry may represent a marker to identify patients with myeloid dysplastic features independent of the administered therapy. Methods: Starting from January 2022, we prospectively enrolled 50 adult patients (median age 66 years old, range 48-83) affected by plasma cell dyscrasias as follows: 10 MGUS, 10 remission-MM, and 30 active newly diagnosed MM patients treated upfront with a daratumumab containing regimen. As a control group, we collected samples of 23 age-matched healthy donors (median age 50 years old, range 28-66). The EDTA samples of peripheral blood were analyzed by flow cytometry using the following panel of monoclonal antibodies: HLA-DR, CD14, CD15, CD45, CD71, and CD117. CD15+CD71+CD117+ cells were considered myeloid precursors. The differences among means were studied through ANOVA, and the differences between the subgroups through Tukey’s multiple comparisons tests. A value <.05 was considered significant. The median time of follow-up was 13.8 months. Results: We found a progressive increase of circulating CD15+CD71+CD117+ cells in MM patients (median 0.16%, range 0.02-0.23%) compared to MGUS (median 0.01%, range 0.002-0.2%) and healthy donors (median 0.001%, range 0.001-0.002%), p<0.001, ANOVA. A cut-off of 0.05% CD15+CD71+CD117+ cells, identified by ROC analysis (AUC 0.89, p<0.001), was used to investigate any difference in outcome among MM patients. We found that patients with high CD15+CD71+CD117+ cells (defined as 0.05% or more) had higher ISS (p=0.04), lower hemoglobin levels at diagnosis (p=0.04), and carried more frequently high-risk FISH (p=0.06) compared to patients with low CD15+CD71+CD117+ cells. After a median follow-up of 13 months, univariate survival analysis failed to identify high CD15+CD71+CD117+ cells as a predictor of either progression or overall survival. Summary/Conclusion: CD15+CD71+CD117+ myeloid precursors are increased in MGUS and MM patients compared to healthy subjects without any apparent effect on clinical outcomes. More extensive series and longer follow up are required to investigate their prognostic role in MM outcome and the relevance in MGUS. Keywords: Myeloid differentiation, Myelodysplasia, Multiple myeloma, Flow cytometry