Clemens Schmitt, MD of the Max Delbruck Center for Molecular Medicine, Berlin, Germany discusses the ongoing debate about the two biologies of diffuse large B-cell lymphoma (DLBCL), i.e. cell of origin discussion about germinal center B-cell (GCB) vs activated B-cell (ABC) subtype. They differ biologically and therefore this may be of significance to finding targets. For example, in the ABC subtype there is an enrichment of NF-κB hyper activating mutations. However, the clinical reality is that, for example, targeting the B-cell receptor NF-κB signaling cascade with a BTK inhibitor such as ibrutinib, may give some advantage but there are many activating mutations downstream of the pathway, meaning that the situation is quite complex. In terms of IDH2, some patients may benefit from a targeted approach but also patients without the mutation or patients with the GCB subtype.
Recorded at the 2016 International Workshop on Non-Hodgkin Lymphoma (iwNHL) meeting held in San Diego, CA.