P160 | PROGRESSION FROM MGUS THROUGH SMOLDERING MYELOMA IS ASSOCIATED WITH ACQUISITION OF IMMUNE-SENESCENCE PHENOTYPE IN PERIPHERAL BLOOD

The role of B cells, in contrast to T cells, in MGUS progression is poor investigated. Recently, the expansion of CD71+ neutrophils has been defined as hallmark of ageing. We prospectively enrolled 133 adult patients (median age 66 years old, range 48-83) affected by plasma cell dyscrasias as follows: 26 MGUS, 20 smoldering (sMM), and 87 active MM to measure the amount of circulating CD15+CD71+CD117+ myeloid precursors and memory B cells, to investigate if immune-senescent compartments are associated with MGUS progression through active MM. We found a progressive increase of circulating CD15+CD71+CD117+ cells in MM patients (median 0.16%, range 0.02-0.23%) compared to sMM (median 0.08%, range 0.02-0.2%) and MGUS (median 0.01%, range 0.002-0.2%) , p<0.001. 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 level at diagnosis (p=0.04) and carried more frequently high-risk FISH (p=0.06) compared to patients with low CDs with low CD15+CD71+CD117+ cells. We found a redistribution of B cell subsets with reduced pool of IgM+ CD27- naïve B cells, increased frequencies of IgM+ memory B cells (p<0.001), known for their association to chronic inflammation, aging and senescence, due to increased migratory capacity and differentiation into antibody-secreting cells. In the progression from MGUS through sMM and MM we found a progressive reduction of class-unswitched B-memory, correlated to expansion of myeloid precursors, independently from chronological age of patients. In obese subjects (BMI>30) both CD15+CD71+CD117+ and IgM+ memory B cells were increased. Myeloid and B-cell subsets display ageing phenotype in the progression from MGUS through MM, however external factor, like obesity, could accelerate immune-senescence. Larger series and longer follow up are required to investigate their prognostic role in MM outcome. Acknowledgments: this work is funded by the European Union - Next Generation EU - PNRR M6C2 Investimento 2.1 “Valorizzazione e potenziamento della ricerca biomedica del SSN" - Grant n. PNRR-MAD-2022-12376660 – CUP Master: G95E22001070007