PS1409 RESULTS OF THE FREQUENCY AND CAUSES OF DISCONTINUATION OF THE SUCESIVE THERAPEUTIC LINES IN PATIENTS WITH MULTIPLE MYELOMA: REAL LIFE DATA FROM A SINGLE SPANISH CENTER
Authors: Campo M.A. Legarda, M.J. Cejalvo Andujar, L. Rubio Lopes-García, M. Jiménez Castillo, E. Francés Aracil, P. Ribas García, L.E. Marriaga Ospino, E.M. Donato Martín, M. Fernández Zarzoso, M.J. Sayas Lloris, M.J. Fernández Llavador, J. Marco Buades, A. Tolosa Muñoz, M.L. Juan Marco, A. García Feria, M.T. Gimeno Brosel, E. Gómez Beltrán, J. De La Rubia
Journal: HemaSphere (2019)

Background: Currently available therapeutic strategies are dramatically changing Multiple Myeloma (MM) clinical landscape, thus making crucial the identification of novel prognostic tools to predict both response to therapy and outcome. Cytogenetic abnormalities have a well-established prognostic value, with their assessment mandatory at diagnosis. Similarly, FACS analysis is also recommended for a correct clinical management of MM. Among cytofluorimetric features of tumour cells (CD138+), CD56 expression is emerging as novel biomarker for traditional as well as novel agents-based therapies used for newly diagnosed MM patients (NDMM) as induction regimens. Aims: A retrospective analysis of NDMM patients admitted at our centre from 2010 to 2018 was performed to assess prognostic significance of Bone Marrow Plasma Cells cytofluorimetric features. Methods: 136 NDMM patients (median age 68, range 32–85; males 50%) with available cytofluorimetric analysis (CA) were studied. Most (96%) received PI-based induction therapies, including ASCT in 36 cases (26%). Extramedullary disease (EMD) was observed in 10% of patients. Median follow-up was 30 months (range 2–94). Cytogenetic risk (CR), evaluated by standard karyotype analysis as well as FISH assay including t(11;14), t(4;14), del13q and del17p, was available in 103 cases (76%). Among these patients, 33 (32%) were classified as high risk (HR). Based on 8-color flow-cytometry analysis, NDMM patients were considered as expressors (E) or dim/non expressors (NE), regarding to cluster of differentiation (CD) expression. Correlation between categorical variables was assessed by Chi-Square or Fisher's exact test. Cumulative survival was estimated by Kaplan-Meier method, with log-rank test. Response rates (grouped as responders if ≥PR - 83% of patients - and non-responders if ≤SD - 17% - according to IMWG criteria) as well as survival outcomes (PFS, OS) were analyzed in multivariate models by logistic regression and Cox Proportional Hazard regression. Results: Dim/no CD56 expression was associated with EMD phenotype (p = 0.010). By using logistic regression analysis, higher CD56 levels were associated with greater probability of response after induction therapy (odds ratio, OR = 12, p = 0.001), independently of CR; high CR was associated with increased rate of non-responders/refractory patients (OR = 0.18, p = 0.026). Model was adjusted by age and sex. PFS was significantly shorter (median 1.8 vs 3.1 years, p = 0.003) in the CD56-NE vs CD56-E group, a result confirmed in a multivariate model considering age, CR and ASCT (p = 0.002). Although among HR patients (n = 33) OS was longer in the CD56 E-group, difference was not significant (p = 0.064). In patients not undergoing ASCT, multivariate model (adjusted by age and CR) showed a reduced risk of death in the CD56 E-group (p = 0.017).Summary/Conclusion: Overall, our data confirm the association between CD56 dim/no expression and EMD, in line with CD56 reported biological role as adhesion molecule. PFS analysis of PI-treated patients identifies CD56 dim/no expression as a negative prognostic marker and affects OS in patients not undergoing ASCT, thus confirming previous observations where ASCT could overcome its adverse prognostic impact. Overall our study indicates the independent impact of CD56 expression on both ORR and survival outcomes, regardless of CR status. Further evaluations are warranted to fully incorporate this biomarker in a more useful score system, helping clinicians in choosing the more appropriate therapeutic strategy for NDMM patients.