A MYC-rearrangement is a negative prognostic factor in stage II, but not in stage I diffuse large B-cell lymphoma

MYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III–IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I–II is unclear. Therefore, we assessed the impact of MYC-R on progression-free survival (PFS) and overall survival (OS) in LS DLBCL patients at the population level. We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022. Stage I patients with (n = 83, 11%) and without (n = 650, 89%) a MYC-R had similar 2-years PFS (89% and 93%, p = 0.63) and OS (both 95%, p = 0.22). Conversely, stage II DLBCL patients with a MYC-R (n = 90, 13%) had inferior survival outcomes compared to stage II patients without a MYC-R (n = 611, 87%) (PFS 70% vs. 89%, p = 0.001; OS 79% vs. 94%, p < 0.0001). Both single MYC-R (single hit, n = 36) and concurrent BCL2 and/or BCL6 rearrangements (double/triple hit, n = 39) were associated with increased mortality and relapse risk. In conclusion, in stage II DLBCL a MYC-R is negatively associated with survival. In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.

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