Diffuse Large B-Cell Lymphoma: Challenging Patients and Evolving Management

Dr. Brian Link, Professor of Internal Medicine at the University of Iowa’s Holden Comprehensive Cancer Center, spoke with CancerNetwork at the 2013 ASCO meeting about topics in diffuse large B-cell lymphoma (DLBCL). Here he discusses key challenges in the management of very elderly patients with DLBCL, and how management of DLBCL overall is evolving.

Cancer Network: What are some key challenges in the management of very elderly patients with DLBCL, and how can they be addressed?

Dr. Link: Interestingly, despite the fact that we know that for fit patients, the best therapy for diffuse large B-cell lymphoma is an anthracycline-containing combination of chemotherapy, even in fit elderly patients, population studies both in the United States as well as from other European countries routinely document the fact that, in the general elderly population, there are a substantial number of patients who don’t get anthracycline-based combination immunochemotherapy, and indeed there’s perhaps 25% to 35% of patients who don’t receive any form of intravenous chemotherapy.

The first challenge in addressing elderly patients with diffuse large B-cell lymphoma is to attempt to overcome the concern for giving anthracycline-based immunochemotherapy whenever possible. I do try and give anthracycline-based immunochemotherapy even if I feel the need to do it at reduced doses. If, for some reason, I feel I just can’t feel comfortable giving anthracycline-based chemotherapy, there is plenty of evidence to suggest that non–anthracycline-based immunochemotherapy combinations can still be effective and aren’t futile.

So, I think our first step is to get over the notion that, although R-CHOP might be the best therapy, it’s not the only therapy, and if, for whatever reason, you don’t feel comfortable treating an elderly patient with anthracycline-based immunochemotherapy, other options still add benefit.

Cancer Network: Are there any options that are particularly promising in this population?

Dr. Link: No, there’s been a surprising lack of controlled studies, prospectively done, in this patient population, but again, the population-based studies, retrospective analyses suggest that if you lump non-anthracycline combinations together, they’re still potentially effective.

Cancer Network: Is there anything promising in the way of biomarkers or genetic characteristics that could inform the management of patients with DLBCL?

Dr. Link: Clearly, the next step forward in this second decade of our century will come from the realization that diffuse large B-cell lymphoma is really a very heterogeneous group of diseases, and recognizing subsets within that disease will allow us to target specific subsets. That’s already happened. We do have biomarkers for which there are good targets, and as yet they haven’t been clinically validated to the point where we’re ready to say “for this subset, treat differently, for that subset, treat differently.” I think the most promising opportunity is in lumping the diffuse large B-cell lymphomas into the cell of origin categories of GCB [germinal center B-cell like] type vs non-GCB type or ABC [activated B-cell like] type, where some of these unique pathways can be grouped together. But it’s hard to imagine that with our currently available experimental agents that target NF kappa B or that target B-cell receptor signaling pathways that ultimately we won’t be able to individualize those further. So, many promising opportunities [that are] not yet validated as of this spring, but I wouldn’t be surprised if, within the next year or two, something’s validated.