Diffuse large B-cell lymphoma with MYC gene rearrangements

CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial

“…MYC gene rearrangements and high MYC protein overexpression (defined as ≥ 40% of lymphoma cells) are estimated to be present in approximately 10% and 30% of all newly diagnosed DLBCL patients, respectively, 2 , 16 , 20 – 22 with similar rates also reported in relapsed patients. 13 The emergence of MYC alterations as defining features of DLBCL is highlighted in the current National Comprehensive Cancer Network (NCCN) guidelines on non-Hodgkin lymphoma and the most recent World Health Organization (WHO) revisions on lymphoma classifications.…”

“… 10 Numerous studies in the past decade have demonstrated that alterations of MYC in DLBCL patients, defined as rearrangements or amplification of the MYC gene and/or MYC protein overexpression, confer dismal outcomes and poorer prognoses. 2 , 11 – 17 MYC is a transcription factor responsible for many cellular functions including cell proliferation and growth, and the upregulation of MYC is a common driver event in multiple human cancers. 2 , 3 , 18 , 19 Certain rearrangements of MYC [determined by fluorescent in situ hybridization (FISH)] lead to activation of the gene, increased protein expression [determined by immunohistochemistry (IHC)], uncontrolled cell growth, and increasingly aggressive disease.…”

“… 2 , 3 , 18 , 19 Certain rearrangements of MYC [determined by fluorescent in situ hybridization (FISH)] lead to activation of the gene, increased protein expression [determined by immunohistochemistry (IHC)], uncontrolled cell growth, and increasingly aggressive disease. 2 …”

MYCgene rearrangement in diffuse large B-cell lymphoma does not confer a worse prognosis following dose-adjusted EPOCH-R

“…Specific molecular events such as MYC rearrangement ( MYC -R), which occurs in a number of B-cell lymphomas including DLBCL and high-grade B-cell lymphoma not otherwise specified (NOS), is associated with a worse prognosis [1–5]. In several retrospective studies, the presence of a MYC -R alone termed ‘single-hit’ or in combination with a BCL2 or BCL6 translocation termed ‘double-hit’ were associated with significantly lower 2-year survivals ranging from 35 to 59% following standard R-CHOP chemotherapy [6–8]. However, patients with MYC -R tumors who receive more intensive chemotherapy appear to have a significantly improved progression-free survival (PFS) compared to those who receive R-CHOP chemotherapy [9,10].…”

Diffuse large B-cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up

“…Management of DLBCL patients with MYC rearrangement 4.8.1. Patients of this subgroup usually have an aggressive clinical course, and CHOP-R alone would give a poor outcome, especially in cases when MYC rearrangement is combined with mutated BCL-2 or BCL-6 (double hit) or mutated BCL-2 and BCL-6 (triple hit) (EL-3)[2829]4.8.2. For double hit (translocated MYC and translocated BCL-2 ), R-EPOCH for 6 cycles plus CNS prophylaxis is recommended (EL-3).…”