Myc Translocation Is an Adverse Factor Redefining High-Risk Multiple Myeloma

Background: Multiple myeloma is an incurable hematological malignancy with heterogeneous biology and clinical outcomes. The criteria of risk stratification has not been unified yet, which mainly depended on cytogenetic abnormalities (CAs). In our previous study, Myc translocation (T-Myc) was strongly correlated with adverse outcome in newly diagnosed multiple myeloma (NDMM). Thus, further predictive value of Myc translocation and its role in redefining high-risk MM were explored.

Methods: The clinical data of NDMM patients at our hospital from May 2009 to May 2021 were retrospectively analyzed. CAs including Myc translocation and conventional CAs were detected by fluorescence in situ hybridization (FISH). Treatment regimens and survival data were collected.

Results: A total of 302 patients were included in this study. The proportions of T-Myc and other Myc abnormalities (OA-Myc) (amplification, deletion, complex aberrations, etc.) were 14.2% (43/302) and 11.0% (33/302) respectively. The baseline clinical characteristics, treatment regiments, and front-line regimen response were comparable in groups of T-Myc, OA-Myc and non-Myc abnormalities (P > 0.05). The median progression-free survival (PFS) in patients with T-Myc, OA-Myc and non-Myc abnormalities were 16.4 months, not achieved (NA) and 23.4 months (P=0.36), and the median overall survival (OS) was 23.6 months, NA and 60 months, respectively (P < 0.001). T-Myc rather than OA-Myc was an independent unfavorable factor for OS. Twenty-six among forty-three (60.5%) T-Myc patients coincided with other high risk (HR) CAs including the most common 1q21 amplification (53.5%), followed by 17p deletion (16.6%). Moreover, the median OS in patients without HRCA and patients with single HRCA was 61.83 months and 61.23 months, whereas patients with T-Myc only, those with 2 or more HRCAs, or those with T-Myc plus other HRCAs presented significantly shorter median OS (31.47 months vs 28.33 months vs 23.33 months respectively, P < 0.001).

Conclusions: The cytogenetic abnormalities in MM patients are very complex. Myc translocation rather than other abnormalities is an independent prognostic factor. Single HRCA without Myc translocation is not translated into inferior survival. We here suggest that Myc translocation should be included as a new and crucial adverse factor in risk stratification model of NDMM. Patients with double or multiple conventional HRCAs or Myc translocation are classified as the truly high-risk population.

Key words: multiple myeloma, Myc translocation, high risk, double hit, risk stratification

No relevant conflicts of interest to declare.