Pb2113 Impact of Clonal Heterogeneity in Complex Karyotypes of Multiple Myeloma Patients With First Line Bortezomib‐based Therapy: A Single‐institution Experience in Bulgaria

Abstract

Background:Multiple myeloma (MM) is genetically heterogeneous with varied clinical outcomes, primarily due to the coexistence of diverse numerical and structural cytogenetic abnormalities (CA). The data about prognostic significance of clonal evolution and cumulative effect of multiple high‐risk (HR) CA in complex karyotypes (CK) of MM patience (pts) is controversially.Aims:1) to make cytogenetics profiling of CK in our MM pts with first line bortezomib‐based therapy (BBT); 2) to find relationship between clonal heterogeneity in CK and therapeutic response and OS of our MM pts.MethodsWe examined the cytogenetic features in 78 pts with newly diagnosed MM using conventional cytogenetics and molecular‐genetics (for t(4;14)/MMSET‐IgH) analysis for 5 years (2014‐2018) in SBALHZ–Sofia, Bulgaria. The followed CA were considered as clinically relevant: hyperdiploidy, hypodiploidy, gap 1q, ‐13/13q‐, ‐17/17p‐, t(4;14), t(11;14). OS was calculated using Kaplan‐Meier estimates.Results:The CK was occurred in about 38% (30/78) of our pts: in 77% (23/30) with hyperdiploidy and in 23% (7/30) without it. The features of clonal evolution (2 or more aberrant cell clones) were defined in 57% (17/30) CK and predominantly were connected with hyperdiploidy (15/17). The coexistence of 2 or more adverse prognostic CA was defined in 60% (18/30) CK. The proportion of pts with normal karyotype (NK) who achieved CR and VGPR was two and half times more than in pts with CK (16,7% vs 41,7%). The autologous stem cell transplantation (ASCT) was applied at 26,7% (8/30) pts with CK and 31% (15/48) pts with NK. We have not found a statistically significant difference in the OS of our pts with signs of clonal evolution or multiple HR CA in CK compared to other CK pts. Although the mean OS of pts with HR CA or clonal heterogeneity in CK without ASCT was lower than OS of CK pts treated with ASCT, the difference in OS wasn’t statistically significant (19.0 mths vs 25.2 mths, p = 0.419). Only groups that stratified according to Mayo Stratification of Myeloma (with HR CA, intermediate‐risk CA and standard‐risk CA) had a statistically significant OS difference (p < 0,006).Summary/Conclusion:We have not found cumulative adverse effect of multiple HR CA or signs of clonal evolution in CK on OS of our MM pts.