Bendamustine for indolent lymphoma reduces relapse after 10 years

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Published: 5 Jun 2017
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Dr Mathias Rummel - University of Giessen, Giessen, Germany

Dr Rummel speaks with ecancer at ASCO 2017 about 10 years of data gathered from across German clinics from patients with indolent lymphoma who were treated with bendamustine rituximab as a first line therapy.

Compared to alternative R-CHOP regimens, the bendamustine data shows equivalent overall survival at 10 years, with less patients relapsing, later.

 

We brought this up to the community fifteen years ago and we started in the year 2000 with a phase II study and in the year 2003 we initiated a randomised comparison of bendamustine rituximab against CHOP rituximab which was, in the old days, the standard treatment. We have reported the results of that study in the plenary session of ASCO 2012, so five years ago at the same meeting and then published it in 2013. These final results focussed on the difference in progression free survival showing that bendamustine rituximab had a much better disease control than CHOP rituximab in our datasets. However, many people debate if progression free survival is really the perfect endpoint; of course we would like to see in the end the overall survival. But in this kind of disease, which is a low grade or indolent lymphoma, you need a much longer time to have a mature result for overall survival. Fortunately we were able to present mature long-term results at this ASCO meeting.

Which takes us to the ten year survival data, if you could tell us more about that now?

We have presented here the ten year median observation follow-up for the survival data. This was an investigator initiated study group so we still have contact to the study sites which is a big advantage. Sometimes the study is closed and then you have problems to follow-up the patients but here it is different because we always have ongoing contact and even we have some more further study protocols where we work together in Germany. We decided to ask three simple questions after ten years: are the patients alive or have they passed away, if so when and why? The second question: was there any need for a second line treatment after the first line treatment in that study? And third question: have you observed any secondary malignancies in one of these patients? So three simple questions made it very easy for the doctors to answer and therefore we have very reliable and good quality of data because these three questions were answered. So here I reported time to next treatment: 77 patients out of 215 who were initially treated with bendamustine rituximab had a second line treatment and 109 in the CHOP-R group. The curve for the interval time to next treatment is highly statistically significant, better for the bendamustine rituximab treated group. By far less patients needed a second line treatment during their life again reflecting that bendamustine rituximab has a very good control of the disease, even better than CHOP-R had in this study.

Then we answered the second question, how many patients are alive. This is one of the very few studies which were initially done as a prospective trial reporting ten year overall survival data. We can say 70% of the patients who were treated initially with bendamustine rituximab are alive after ten years and after CHOP-R 66% are alive. Of course this is not a statistically significant difference so we have to say there is no difference in overall survival. 61 patients died in the BR arm and 70 patients died in the CHOP-R arm during that ten years. Most of the patients who died are in the group who have not responded initially to the first line treatment, this was only 9% of the patients but out of this small group of 34 patients, 24 have died. So this is a very important reason for the death that we have observed, again showing and confirming what everybody else found - when you have not responded as a patient to the first line treatment you have a very poor prognosis.

The other important message is that we have to explain to our patients when they ask that question, ‘What is my life expectancy?’ Then we always go back to what we have heard in the textbook of haematology or in some very old reviews and we start to say, ‘The median survival is around ten, twelve years,’ and so on. At least this is one very good piece of information now. In our prospective trial we really can say if you are treated with BR or with CHOP-R your life probability at ten years is 70% or 66%, so far longer than the median. The median is probably at fifteen years or even longer. So that’s also a very valid and very meaningful observation.

Then we ask for the secondary malignancy because this is still debated. Is the old bendamustine a factor for an increased incidence of secondary malignancies. In particular you may think MDS or acute leukaemia happens more often after treatment with bendamustine. It was not the case in our study and, as I told in the beginning of this interview, this was the third question, very easy – was there a secondary malignancy or not? Still if we don’t get every data out of the community, the study sites, still it would be the same for both treatment arms. So I am quite confident that I can report the data and we reported 37 patients were reported to have secondary malignancies after BR and 40 after CHOP-R. So we can conclude with BR there was no increased incidence for secondary malignancies. This was a little bit different to the abstract which was the prior abstract when I was here presenting because the American study, the prior trial, reported a higher incidence of secondary malignancies. However, they explained it that it was more the reason for squamous cell carcinoma of the skin and basal cell carcinoma, usually not life threatening diseases but this was a signal in that study. Again I have to say I have not seen that in our case report forms when we ask our doctors in Germany.

I suppose all we can do now is sit back and wait for fifteen year data come ASCO 2022?

Probably the quality and type of information will not change. I don’t think that there will be so much different information in five years from now. But yes we will do it, absolutely, because we still have this good network and we can still keep on asking the doctors. Also we asked our study sites to report deaths of the patients even if we don’t ask for it. So they will report it and again we will make another update, yes, for sure. So again we will address that question five years from now approximately for secondary malignancies, for overall survival and time to next treatment.

But the main message, what I have shown today, I don’t think this will be changed. There is no reason to believe that in five years from now it’s very much different, that we have to open the chapter again, I don’t think so. With these ten years results it’s very mature and very reliable data.