A central theme of the congress was abstract contributions with reference to the recently published genomic in-depth analyses of lymphoma samples from large DLBCL patient cohorts, which led to the classification of novel molecular “clusters” (Shipp lab; Chapuy et al., Nat. Med. 2018 [8
]) or novel molecular subtypes (Staudt lab; Schmitz et al., New Engl. J. Med. 2018 [9
]). In the expectation that these novel subgroups not only have prognostic or R‑CHOP-predictive meaning, but also provide information to select differential targeted treatment options, it will be important to simplify the complex molecular designation of a given patient to such cluster/subtype classification systems in clinical practice. A systems-overarching algorithm based on a 55-gene classifier was introduced by abstract number 551 (Esfahani et al. [10
]). A particular strength of this approach was its suitability for both lymphoma biopsies and liquid biopsies, i.e. the analysis of circulating tumor DNA (ctDNA) from peripheral blood plasma samples. Interestingly, liquid biopsies also proved to be instrumental for a cell-of-origin designation as GCB or activated B‑cell (ABC) subtype at a highly concordant level with transcriptome-based lymphoma analyses (see also abstract number 490, Tabari et al. [11
]). Moreover, the authors demonstrated how reliably ctDNA analyses conducted in liquid biopsies may actually detect prognostically relevant single-nucleotide variants (such as p53 mutations) or translocations (such as myc rearrangements). Moreover, those prominent tumor suppressor and oncogenic alterations were exploited for the quantitative estimation of subclone dynamics, including the burden of minimal residual disease, in the course of disease (see also abstract number 921 by Rushton et al. [12
]). Equally interesting were complex studies that addressed the lymphoma microenvironment, thereby unveiling prognostic contributions of distinct normal bystander cell compositions in the micro-milieu independently of the above-mentioned lymphoma subtypes (abstract number 656 by Cerchietti et al., [13
]). A similar strategy even linked so-called eco systems, complex groups of lymphoma and normal cell populations characterized by certain activity states, to long-term survival (abstract number 655 by Steen et al. [14
]). In essence, some of those nucleic acid-based approaches may rapidly impact on clinical practice. As a perspective, the retrospective re-analysis of the numerous negative large-scale phase III “R-CHOP ± X” trials by simplified gene classifiers may unveil hitherto unknown but actually benefitting subgroups—and, thereby, might provide the basis for confirmatory prospective trials in those genetically determined patient groups.