Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable

Abstract

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). Yet, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with double hit lymphoma (DHL), all treated with either R-CHOP or intensive induction therapy. For SHL and MYC amp patients, the 2 year progression free survival rate (2yPFS) was 49% and 48% and 2 year overall survival rate (2yOS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2yPFS (59% vs. 23%, P=0.006) but similar 2yOS as compared with SHL patients receiving R-CHOP. SHL DLBCL patients treated with R-CHOP, but not intensive induction, experienced significantly lower 2yPFS and 2yOS (p<0.001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.

Stratification by MYC expression has prognostic impact in MYC translocated B‐cell lymphoma—Identifies a subgroup of patients with poor outcome

“…DH had no additional prognostic effect compared to SH in this study. This is in accordance with other previously published studies which could not demonstrate an additional prognostic effect of DH compared with SH in large cohorts of patients with DLBCL and MYC translocation 2,3,6. A recent study of patient samples from a large randomized trial of LBCL also found a prognostic effect of both SH and DH 4.…”

“…According to WHO, the prognostic importance of MYC translocation in LBCL is however still not sufficiently clarified. So‐called single hit MYC translocation (SH) without concurrent BCL2 and/or BCL6 rearrangements has also been associated with inferior survival, and in addition, we and others described particularly poor outcome both in patients with MYC‐SH or DH with an immunoglobulin‐( IG ) MYC translocation partner gene . In addition, stratification of patients with MYC ‐SH and DH translocations according to MYC protein expression level and/or BCL2 expression level has been suggested to impact patient survival in few studies.…”

Double hit and double expressors in lymphoma: Definition and treatment

“…The most frequently observed derangement leading to MYC protein overexpression involves the translocation of MYC to the immunoglobulin gene (IG) locus. [22][23][24][25][26] The MYC-IG rearrangement is the hallmark of BL and serves as a defining characteristic in approximately 60% of HGBL cases and in a minority of cases of DLBCL.…”

Chromosomal abnormality variation detected by G‐banding is associated with prognosis of diffuse large B‐cell lymphoma treated by R‐CHOP‐based therapy

“…Although double-hit or triple-hit B-cell lymphomas are well-known with worse prognosis, previous studies concerning the prognostic impact of a c-MYC rearrangement alone have been controversial. Some studies demonstrated that a c-MYC rearrangement leads to poor prognosis even without BCL2 or BCL6 rearrangements [22,23], while a c-MYC rearrangement alone did not show significant prognostic impact in other studies [24,25]. The rearrangement of BCL2, BCL6, or PAX5 alone has not been associated with worse outcome in DLBCL patients [26,27], while the prognostic impact of CCND1 rearrangement in DLBCL has been controversial [28].…”