The impact of CD56 expression in smoldering Multiple Myeloma

Background The identification of risk factors for progression is critical in the clinical management and appropriate follow up of patients with SMM. Several prognostic score identify in SMM patients the main risk factors for progression to MM, but new parameters to identify possible progression in SMM need to be defined. The aim of this study was to investigate the possible role of the immunophenotype and the role of CD56 expression as risk factor for progression. Method We retrospectively evaluated a cohort of SMM patients admitted to a single haematological center between 2014 and 2019. We analyzed a total cohort of 80 patients diagnosed with SMM according to the IMWG diagnostic criteria. All patients analysed underwent to Bone Marrow (BM) examination and imaging evaluation was performed. Both immunophenotypic and FISH analysis were performed of BMPCs. Results Overall 25 patients of the entire cohort progressed to MM with a median the time to progression (TTP) of 24 months. Firstly, we validated the currently score of progression in our cohort. We found that percentage of BMPCs and presence of immunoparesis were significantly correlated with progression to MM (p<0.05 for each variable). Afterwards, we confirmed the SMM risk stratification models. “Pethema” (p=0.0006), Mayo score (p=0,0092), “20-2-20” score (p=0.0001) and also the “Danish score” (p= 0.003) turned out statistically significant. Then, we investigate the possible role of CD56 expression in the risk of progression, by flow cytometry analysis and its association with a variety of clinicopathological parameters. We found that the median TTP in CD56- SMM patients was shorter than TTP in CD56+ ones (11 months vs 31 months, p = 0.08). Moreover CD56- patients progressed without a significant increase of the Monoclonal Component as compared to CD56+ ones (p=0.0062). This was also confirmed by the increase in the bone marrow infiltrate value which was statistically significant only in the CD56+ group (p:0.0006 vs p:0,17). The same result was also assessed with the Beta2microglobulin value (p: 0,001 vs p: 0,13). Finally, we compared CD56 expression to cytogenetic abnormabilities and we found a relationship between CD56 expression and the hyperdiploidy, a good prognosis factor. CD56-SMM patients had a significant lower presence of hyperdiploidy as compared to those with CD56+ BMPCs (p=0.04). Also this result reinforces the thesis that lack of CD56 is associated with a poorer prognosis and could be a possible factor for a more aggressive disease associated with unfavorable prognostic parameters. Conclusion In conclusion, our data confirmed that in SMM patients the factors, which mostly impact on the short-term risk of progression to active MM, are the entity of the PCs infiltrate and the immunoparesis. Therefore, our study identified CD56 as a possible marker of poor prognosis in patients with SMM. Indeed the lack of CD56 expression could be a factor for a more aggressive disease regardless to the tumoral burden. The identification of risk factors for progression is critical in the clinical management and appropriate follow up of patients with SMM. Several prognostic score identify in SMM patients the main risk factors for progression to MM, but new parameters to identify possible progression in SMM need to be defined. The aim of this study was to investigate the possible role of the immunophenotype and the role of CD56 expression as risk factor for progression. We retrospectively evaluated a cohort of SMM patients admitted to a single haematological center between 2014 and 2019. We analyzed a total cohort of 80 patients diagnosed with SMM according to the IMWG diagnostic criteria. All patients analysed underwent to Bone Marrow (BM) examination and imaging evaluation was performed. Both immunophenotypic and FISH analysis were performed of BMPCs. Overall 25 patients of the entire cohort progressed to MM with a median the time to progression (TTP) of 24 months. Firstly, we validated the currently score of progression in our cohort. We found that percentage of BMPCs and presence of immunoparesis were significantly correlated with progression to MM (p<0.05 for each variable). Afterwards, we confirmed the SMM risk stratification models. “Pethema” (p=0.0006), Mayo score (p=0,0092), “20-2-20” score (p=0.0001) and also the “Danish score” (p= 0.003) turned out statistically significant. Then, we investigate the possible role of CD56 expression in the risk of progression, by flow cytometry analysis and its association with a variety of clinicopathological parameters. We found that the median TTP in CD56- SMM patients was shorter than TTP in CD56+ ones (11 months vs 31 months, p = 0.08). Moreover CD56- patients progressed without a significant increase of the Monoclonal Component as compared to CD56+ ones (p=0.0062). This was also confirmed by the increase in the bone marrow infiltrate value which was statistically significant only in the CD56+ group (p:0.0006 vs p:0,17). The same result was also assessed with the Beta2microglobulin value (p: 0,001 vs p: 0,13). Finally, we compared CD56 expression to cytogenetic abnormabilities and we found a relationship between CD56 expression and the hyperdiploidy, a good prognosis factor. CD56-SMM patients had a significant lower presence of hyperdiploidy as compared to those with CD56+ BMPCs (p=0.04). Also this result reinforces the thesis that lack of CD56 is associated with a poorer prognosis and could be a possible factor for a more aggressive disease associated with unfavorable prognostic parameters. In conclusion, our data confirmed that in SMM patients the factors, which mostly impact on the short-term risk of progression to active MM, are the entity of the PCs infiltrate and the immunoparesis. Therefore, our study identified CD56 as a possible marker of poor prognosis in patients with SMM. Indeed the lack of CD56 expression could be a factor for a more aggressive disease regardless to the tumoral burden.