Advances in treatments for haematologic malignancies from the Sarah Cannon Research Institute presented at ASH 2012 (3/5)
Dr Ian Flinn – Sarah Cannon Research Institute, Nashville, USA
Give us an overview of your open-label randomised study of bendamustine and rituximab.
This is known as the BRIGHT trial, I was pleased to be able to chair this trial. It’s a large international trial comparing bendamustine and rituximab to standard chemotherapy, either R-CVP or R-CHOP and this was for patients who have low grade lymphoma or mantle cell lymphoma. A little bit of background: bendamustine and rituximab is a very popular regimen for patients with low grade lymphoma and mantle cell lymphoma; there was a trial that was conducted by the StiL Group, NH01, this trial has been previously presented and showed that there was an improvement in response rate and there was an improvement now in progression free survival. This trial was conducted as a confirmatory trial and the design is a little bit different in the sense that it was designed to get FDA approval of bendamustine and rituximab as front line therapy. So it’s an important difference between the two trials because one was more of an investigator-initiated, co-operative group trial and this was with all the standards that you would expect with most industry sponsored trials necessary for the Food and Drug Administration.
What were the findings and what are the next steps in clinical research?
The interesting findings from this trial, and I should say the trial was designed for non-inferiority so it was based on the complete remission rate and the non-inferiority in the evaluable patient population and it clearly showed that, it hit the primary endpoint. When we looked at subgroups the trend was the same in essentially every subgroup that we could look at; whether you looked at the R-CHOP or the R-CVP, whether you looked at the mantle cell or the follicular, BR was clearly non-inferior and in some populations it was superior. The thing that I think interests many folks is that the combination of bendamustine and rituximab was highly active in mantle cell lymphoma and had a hazard ratio of about 1.5 when you look at R-CHOP, much higher when you looked at R-CVP and R-CVP is probably really not an inferior treatment regimen for patients with mantle cell.
Explain more about the adverse effects?
The other thing that’s interesting about this is the side effect profile. We associate alopecia with R-CHOP, with any anthracycline; we associate mucositis and febrile neutropenia and that’s very much true, this trial showed that. So there was a higher incidence of febrile neutropenia with patients receiving R-CHOP than those patients receiving BR; there was a much higher incidence of neuropathy in both R-CHOP and R-CVP compared to bendamustine and rituximab. The thing that I thought was interesting was that I had expected bendamustine rituximab not to have as much nausea and vomiting and in fact it had as much or greater; when you look at all the adverse events it had more nausea and vomiting despite the use of antiemetics. That’s another question, because I think other people have the same thing – how could that be? We looked at all the antiemetics used and there was nothing dictated in the trial, it was left up to the individual investigator but when we dialled down on the use of 5HT3 antagonists, there was equivalent. We looked at the cycle, we looked at, that it was given in, it all seemed exactly the same across so I can’t explain the difference based on the prophylaxis or treatment of nausea. So I think that was an interesting finding as well.