Targeted molecular signatures of DLBCL and upcoming CheckMate 647 trial for PCNSL and PTL

Bjoern Chapuy, MD, PhD of Dana-Farber Cancer Institute, Boston, MA gives an overview of his talk on targeted molecular signatures of diffuse large B-cell lymphoma (DLBCL). Dr Chapuy points out that DLBCL is thought to be very heterogeneous with multiple copy number alterations, mutations and structural variants and it is important to understand all of these in order to make informed decisions and stratify patients. He goes on to explain that they performed a comprehensive genomic study of two rare patient groups, central nervous system (CNS) lymphoma and primary testicular lymphoma (PTL), with the aim of understanding their dominant genetic signatures. Both cancers harbor complex copy number alterations similar to those seen in systemic DLBCLs but the mechanisms behind them are different. They identified a dominant near uniform activation of Toll-like receptor signaling pathways. They also identified a copy number gain of PD-L1 and PD-L2 and he believes the genetic basis for PD-1-mediated immune evasion is targetable; they tested this in a small number of patients. The dominant genetic signature of PD-1 dysregulation in these two lymphomas and the initial study on a small number of patients, led to the development of a national and international trial in the relapsed/refractory setting, which will open soon (CheckMate 647, NCT02857426).
Recorded at the 2016 International Workshop on Non-Hodgkin Lymphoma (iwNHL) meeting held in San Diego, CA.

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