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Three genetic classifications of the commonest aggressive lymphoma exist and none of them yet decides anyone's treatment. The trial that would change that has not been run.
The obstacles are concrete rather than conceptual. Comprehensive classification needs copy number and structural variants as well as mutations, which routine panels do not generate; a turnaround time short enough to decide first-line treatment in an aggressive lymphoma means days, not weeks; and a proportion of tumours remain unclassified by design. Any trial has to report that proportion honestly, because a classifier that works on two-thirds of patients is a different clinical proposition from one that works on all of them. The training cohorts were also largely of European ancestry, which is a validation gap rather than a flaw.
The piece that turns a research classification into something a trial can use on one person's biopsy, with a probability attached rather than a flat label. It is the reason genetics-directed lymphoma trials became possible at all.
A failure worth reading: the drug worked where patients could tolerate the regimen it was added to, and harmed where they could not. It is the strongest argument in lymphoma for designing first-line combinations around what an older patient can finish.
The genetic nosology that precision-medicine trials in diffuse large B-cell lymphoma now use to pick patients. It gives a mechanism, not just a label: two of the four subtypes point at a drug class that already exists.
One of the two foundational genetic classifications of diffuse large B-cell lymphoma. Neither has yet changed what a patient receives outside a trial, but together they are the reason precision-medicine trials in this disease now select by genetics rather than by cell of origin.
Shares Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX), A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications, Cell of origin (GCB vs ABC), BCL-2 and the tag lymphoma-evidence.
Shares Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX), Genetics and pathogenesis of diffuse large B-cell lymphoma, Cell of origin (GCB vs ABC), BTK (Bruton tyrosine kinase) and the tag lymphoma-evidence.
Shares Genetics and pathogenesis of diffuse large B-cell lymphoma, Cell of origin (GCB vs ABC), BCL-2, Biomarkers are not validated or standardised and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Next-generation sequencing (NGS), Whole-exome & whole-genome sequencing, Biomarkers are not validated or standardised and the tag lymphoma-evidence.
Shares Next-generation sequencing (NGS), Biomarkers are not validated or standardised, Trial design, endpoints and cost, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares CD79b, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma, Non-Hodgkin lymphoma (all types) and the tag lymphoma-evidence.