Researchers led by the University of Leeds have defined a molecular high-grade (MHG) diffuse large B-cell lymphoma (DLBCL) which has particularly poor prognosis. They suggest patients with MHG DLBCL might benefit from intensified chemotherapy or novel targeted therapies.
While conventional cytogenetics identifies some patients with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphomas) who are increasingly treated with more intensive chemotherapy, a more biologically coherent and clinically useful definition of this group has been lacking.
In this latest research, an MHG group (n=83) was identified by applying a gene expression-based classifier to 928 patients with DLBCL from a clinical trial that investigated the addition of bortezomib to standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The prognostic significance of MHG was compared with existing biomarkers.
MYC rearranged and double-hit groups were strongly over-represented in MHG but made up only half of the total. Gene expression analysis revealed a proliferative phenotype with a relationship to centroblasts.
Three-year progression-free survival after R-CHOP was 37% (95% CI 24%-55%) in the MHG compared with 72% (95% CI 68%-77%) for others. Double-hit lymphomas lacking the MHG signature showed no evidence of worse outcome compared with other germinal centre B-cell-like cases.
Presenting the findings in the Journal of Clinical Oncology, the study authors concluded that “MHG defines a biologically coherent high-grade B-cell lymphoma group with distinct molecular features and clinical outcomes that effectively doubles the size of the poor-prognosis, double-hit group”.
They advised that patients with MHG may benefit from intensified chemotherapy or novel targeted therapies.
