The study by Horn et al1 took advantage of a large series of elderly patients (age 61-80 years) homogeneously treated in a prospective trial with CHOP or rituximab plus CHOP (R-CHOP) to analyze the prognostic impact of MYC, BCL2, and BCL6 at both the gene level and the protein level. First, the description of the distribution of the oncogenic events and the deregulation of the protein expression is of great interest. MYC translocation and MYC protein overexpression (. 40%) were detected in 8.8% and 31.8% of the cases, respectively. MYC translocation was associated in doublehit or triple-hit aberrations with BCL2 and/or BCL6 rearrangements in 60% of these cases. MYC overexpression occurred independently of MYC translocation in 30% of the cases. In terms of cell of origin, MYC and BCL2 rearrangements were more frequently observed in GCB-DLBCL and BCL6 translocation was observed more frequently in non-GCB-DLBCL, whereas at the protein level, no significant difference with respect to MYC overexpression was noted between GCB-and non-GCB-DLBCLs. Second, and more importantly for clinical practice, the survival analyses showed that, taken individually, MYC translocations in the whole group of patients as well as MYC, BCL2, and BCL6 protein overexpression in the R-CHOP group were associated with an adverse prognosis, independently of the IPI score (see figure). Moreover, the pattern associating MYChigh, BCL2high, BCL6low, and MYC rearrangement was highly predictive of the prognosis, independently of the IPI score.

Why is this report significant in routine practice for DLBCL patients? The pivotal importance of this report is that the authors identified in elderly patients treated with R-CHOP a worse group within the IPI highrisk group (3-5 adverse prognostic parameters) with 3-year event-free survival and OS of only 15.6% and 41.6%, respectively. Whether these results will also be true in young patients (younger than age 60 years) in whom intensity of treatment may be different still has to be proven.