Myc Translocation Is a Notable Marker on the Development and Relapse of Extramedullary Disease in Multiple Myeloma

Abstract

Objective: To study the cytogenetic characteristics of extramedullary disease (EMD) in patients with multiple myeloma (MM) and the impact on prognosis. Methods: Patients with newly diagnosed MM (NDMM) at Peking Union Medical College Hospital (PUMCH) from June 2007 to December 2019 were recruited. The demographic information, clinical data, fluorescence in situ hybridization (FISH) of marrow and tissue samples and survival outcome were collected for statistical analysis. Results: A total of 439 NDMM patients were divided into non-EMD group (n=339), paraosseous plasmacytoma (EMD-B, n=48), soft tissue involvement (EMD-S, n=33), and relapsed extramedullary disease (EMD-R, n=19). The incidence of EMD was 18.5% (81/439) at diagnosis and 22.8% (100/439) during whole disease process. Bortezomib based regimens as front-line treatment translated into lower relapse rate of EMD compared with old agents such as thalidomide (2.69% vs 6.94%, p=0.057). The median age of three EMD groups was younger than that of non-EMD group (57.2 years vs 61.5 years, P=0.001), while the proportion of IgD type was higher (14.0% vs 6.2%, P=0.028) in EMD group. Elevation of lactate dehydrogenase (LDH)>250U/L was more common (26.0% vs 10.3%, P=0.001) in EMD group, as well as hypercalcemia >2.75mmol/L (15.0% vs 8.0%, P=0.036). In the paired FISH tests of marrow and extramedullary specimens, the percentages of RB1 deletion (n=20, 60.0% vs 20.0%, P=0.013) and Myc translocation (n=12, 44.4% vs 12.5%, P=0.041) were higher in extramedullary tissues. Even at diagnosis, the percentage of Myc translocation of marrow samples in EMD-R group was much higher than that in non-EMD group (55.6% vs 15.5%, P=0.012). The median overall survival (OS) in EMD-S (32 months) and EMD-R (17 months) patients was significantly shorter (both P=0.001) than that of non-EMD patients (60 months). OS in EMD-B vs non-EMD patients was comparable (60m vs 48m, respectively, P=0.672). Conclusion: Bortezomib-based regimens reduce the development of EMD in relapsed MM, suggesting that drug-induced clonal aggressiveness and evolution is less probable. Soft tissue EMD is the real high-risk situation in the era of novel agents. Myc translocation is a notable marker correlated with extramedullary spread and relapse in MM patients.