PF600 IGH TRANSLOCATIONS WITH UNDEFINED PARTNERS ARE ASSOCIATED WITH SUPERIOR OUTCOME IN MULTIPLE MYELOMA PATIENTS

Background: Multiple myeloma (MM) is a genetically complex and heterogeneous disease with multiple genomic events associated with tumor development and progression.Chromosomal translocations into the immunoglobulin heavy‐chain (IgH) locus on 14q32 are the main primary events, occurring in about 50% of total MM cases. Currently, there are five main chromosomal translocation partners involving with immunoglobulin heavy‐chain (IgH), including t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20). However, IgH translocation with undefined partner genes can still be found in 15% of all newly‐diagnosed MM (NDMM) patient, and little is known about their survival. Aims: In the present study, we examined clinical status, as well as genetic features, and their prognostic significance for predicting PFS and OS, in a cohort consisting of 715 patients with NDMM. Specifically, we focused on characterizing the PFS and OS of patients with NDMM and t(14; undefined) translocation. Methods: A prospective non‐randomized clinical study (BDH 2008/02) was conducted at a single center, with a total of 715 NDMM patients included. The median follow‐up time was 45.3 (42.13–48.47) months. Sorted plasma cells(by anti‐CD138‐coated magnetic beads) were analyzed for del(13q14), del(17p), gains of 1q21, IgH split, t(11;14), t(4;14), t(14;16), t(14;20) and t(6;14). K‐M curves for PFS and OS were plotted; univariate analysis and cox proportional hazards model were conducted. Results: There was about 13.6% patients translocation t(14; undefined) positive. Translocations t(4;14) and t(14;16) were classified into one high‐risk group according to IMWG risk stratification. Translocation t(14;20)(0.9%, 3/322) and t(6;14)(0.8%, 2/228) were assigned to the t(14; undefined) group due to their low incidence. Therefore, the whole cohort (n = 715) was divided into four groups: no IgH group (47.7%, 341/715); t(14; undefined) group (13.6%, 97/715); t(11;14) group (17.6%, 126/715); and t(4;14) or t(14;16) group (21.1%, 151/715). The median overall survival (OS) for the four groups was 84.2 [95% confidence interval (CI), 69.7–98.7] months, not reached (NR), 58.7 (95% CI, 41.9–75.5) months, and 44.2 (95% CI, 34.1–54.3) months, respectively, with p values for the t(14; undefined) group compared with no IgH, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022 and 0.001, respectively(Fig 1). In patients receiving bortezomib‐based therapies, the survival prolongation in the no IgH and t(14;undefined) groups was more significant compared with the t(11;14) and t(4;14)/t(14;16) groups. Importantly, in multivariate analysis, translocation t(14;undefined) was an independent predictive factor for OS of MM patients (HR = 0.51, 95% CI 0.30–0.85, p = 0.01). Collectively, our findings indicated the favorable outcome of NDMM in the t(14; undefined) and no IgH groups compared to the t(11;14) and t(4;14)/t(14;16) groups. Summary/Conclusion: In summary, our data confirmed the favorable prognosis of the t(14; undefined) and no IgH groups, especially in the era of novel agents. Most importantly, translocation t(14; undefined) was identified as an independent protective factor for prolonged OS in multivariate analysis. Our study further validated the short survival of patients with t(4;14)/t(14;16), who are generally classified as high‐risk disease; and conversely, indicated that survival of patients with t(11;14) is decreased relative to other patients with standard‐risk disease.