ASCO 2012, Chicago, USA

Changing the standard treatment for lymphoma with bendamustine

Dr Mathias Rummel – Universitaetsklinik, Giessen, Germany



With indolent lymphomas, CHOP-rituximab is actually a standard treatment, you’ve been challenging that, can you tell me why you decided to try something else?

Because CHOP-rituximab has quite a high toxicity, in particular there is a high potential toxicity and CHOP-rituximab was established in the treatment of diffuse large B-cell lymphoma. Everybody is convinced that this is the standard of care, however, there is not such big evidence out there in the literature if this is also the best treatment approach in indolent lymphomas, a disease in which you cannot achieve a cure with a rituximab-CHOP regimen. So that is a question why you really need such an aggressive treatment as a standard treatment approach.

You were using bendamustine, tell me about that agent and what you did with it.

Bendamustine is an agent which was developed fifty years ago in the East part of Germany and it was used in all kinds of non-Hodgkin’s lymphoma. After the reunification of Germany we started to initiate studies with bendamustine, we right away combined it with rituximab and we found a very high response rate in the relapsed disease population. From that phase II study we went directly to the phase III randomised trial in order to compare it to CHOP-rituximab which was, in these days, the standard treatment approach.

Could you describe this trial to me?

We included patients with indolent lymphoma disease which was follicular lymphoma, marginal zone lymphoma, Waldenström’s disease, small lymphocytic lymphoma as well as elderly patients with mantle cell lymphomas. We randomised them between two treatments, bendamustine rituximab, which is BR, against CHOP-R and the primary objective was to compare progression free survival. We have observed a much superior progression free survival, a much longer progression free survival, with BR treatment; the median PFS was 69 months compared to only 31 months after CHOP-R. Not only that bendamustine-rituximab was more effective, it also showed by far a better toxicity profile.

Now toxicities including hematologic and non-hematologic toxicities.

The hematologic toxicity was by far lower after BR, we have observed much less degree of leukocytopenia and neutropenia, less growth factor support was given and also non-hematologic toxicity, in particular the hair loss is important for the patients because not a single patient is experiencing hair loss after BR but you have hair loss after CHOP-R. Then you see, of course, due to the higher hematotoxicity of CHOP-R, you see more infectious complications and also you see more neurotoxicity because vincristine is included in the CHOP-R and you see more stomatitis. So, in summary, the bendamustine-rituximab was better tolerated and also, on the other hand, was more effective.

And could you give me the figures of the progression free survival, what was that?

69 months median progression free survival for BR compared to 31 months after CHOP-R, which is not only highly statistically significant but also on the other side very clinically relevant.

Now very clinically relevant, it seems so, this is a remarkable difference. What are your conclusions about what doctors should be making of this?

I can nothing else conclude that this should be the preferred first line treatment. If you have a first line treatment which is less toxic and more effective, I cannot make any other conclusion than to recommend it as a preferred first line treatment option for all our patients with their disease entities.

So that’s in any form of indolent lymphoma?

Yes.

What’s the take home message, the bottom line message for doctors all around the world?

The doctors around the world should consider if they can use bendamustine-rituximab already in their country and this would be a very good treatment for their patients with that disease. Also, all patients who have been now treated with a regimen like CHOP-R and go into relapse, one also should consider at least in second line treatment the very effective bendamustine plus rituximab combination.