I think this is a really exciting time for patients with diffuse large B-cell lymphoma. We’ve seen over the last thirty years or so just relatively incremental advances with our chemotherapy and we’ve looked at all sorts of different approaches to intensifying our chemotherapy and really haven’t seen any significant improvements except for the addition of rituximab which gives a 16% overall survival benefit at ten years after completion of treatment. So we’ve made some small progress but not massive progress. What we do know is that we are beginning to unravel the biology of diffuse large B-cell lymphoma. We can understand what the disregulated pathways are, what the oncogenic mechanisms are that drive diffuse large B-cell lymphoma and we’re able to divide patients into subsets based upon the molecular aberrations that there are in their individual lymphomas.

So what I talked about was really some of the new drugs that are available that may have specificity in certain types of diffuse large B-cell lymphomas. Broadly, we can divide diffuse large B-cell lymphoma up into a group of patients who have what we call an ABC type diffuse large B-cell lymphoma where they have the molecular characteristics of B-cells that are activated in the bloodstream. There are also this other group of what we called germinal centre like B-cell lymphomas which look like B-cells that are in lymph nodes. Those two different groups, this ABC group and this GCB group, harbour different prognoses. Those patients with ABC type diffuse large B-cell lymphoma tend to do less well than patients with GCB type diffuse large B-cell lymphoma.

There are a number of new drugs that target specific aberrations that we know go wrong in the ABC type and much of the focus of my talk was looking at these new agents and how we can use these new agents to bring up the prognosis of patients with diffuse large B-cell lymphoma who are of the ABC phenotype to those that have the GCB type. So we talked about drugs such as lenalidomide, we talked about drugs such as ibrutinib and some of the other newer pathway inhibitors. We also talked about a drug called bortezomib which we use commonly in multiple myeloma.

So there are ways of modifying these disregulated pathways; there are also different  new antibodies that target some of the proteins expressed on the surface of diffuse large B-cell lymphoma that are very interesting and may potentially add, or perhaps even supersede, the conventionality CD20, which is rituximab. So we talked about mechanisms of action of monoclonal antibodies in lymphoma; we talked about this new generation of anti-CD20 monoclonal antibodies and about some of the studies that are ongoing at the moment, but we also talked about other pathways, other expressed proteins that may be targets for various monoclonal antibodies. We also looked at antibody drug conjugates, so this is a monoclonal antibody with a specific targeting to malignant B-cells that carry a payload of chemotherapy. We’ve used these very successfully in the treatment of Hodgkin’s disease and there are a number of these drugs that are in clinical development at the moment. So they may be able to spare some of the adverse toxicity of chemotherapy.

So there are a lot of exciting things going on at the time in DL B-cell, so there was a lot of ground to cover in the talk.

What kind of response did you receive?

I think people really appreciated the overview that I was able to give because there are so many new agents and so much data out there, I think people appreciated some brief snapshot of what we were able to review, really.

Do you think this is something that will be used in clinical practice?

There are a lot of clinical trials going on at the moment. In the UK we’ve been running the REMODeL-B study which is looking at bortezomib which may have a preferential activity, potentially, for ABC type diffuse large B-cell lymphoma in combination with R-CHOP chemotherapy. We’ve recruited now 1,100 patients who have had real time molecular analysis to be able to stratify patients into these different groups and they’ve been randomised to have conventional R-CHOP chemotherapy or R-CHOP with the addition of bortezomib. So that study has almost recruited and I think we’ll have important outcomes for us to see when the final analysis comes through. There are a number of other studies looking at new agents in combination with R-CHOP, such as ibrutinib and lenalidomide.

So these are not quite prime time yet, but I would say that in the not too distant future our patients with DLBCL, we will understand the molecular aberrations in the individual patient and not only give them conventional R-CHOP chemotherapy but give them a molecularly targeted agent. So it’s not quite there yet but I don’t think it’s too far away.

What would you like doctors to take away from this?

I hope they have gone away with an understanding of what these new agents are, the different pathways that they may affect and the different cell surface markers, for example, that they may affect. So I hope that they’ve gone away with a feeling of understanding of the new molecules, that patient stratification is going to be important and actually I don’t think that we’re going to be using single agent R-CHOP for very much longer.