First results of a prospective bendamustine/rituximab trial in patients with MCL
Dr Mathias Rummel - University of Giessen, Giessen, Germany
We have addressed the question if the two year rituximab maintenance treatment adds something to the efficacy of the first line treatment with bendamustine rituximab in patients with mantle cell lymphoma who are elderly and not eligible for a high dose treatment approach which usually would be the standard treatment.
What kind of results are the group finding?
The rituximab maintenance treatment, which is given for two years every two months, is the standard treatment for other kinds of lymphomas like follicular lymphoma. There was a very important question: is this maintenance also relevant for patients with mantle cell lymphoma because mantle cell lymphoma is very similar to follicular lymphoma, it’s not a disease which you can cure with some high dose chemotherapy and therefore it’s always the aim to prolong disease control. So the question was can we prolong disease control when we add two year rituximab maintenance after the induction treatment with six cycles of bendamustine rituximab.
Did you find an answer?
We found an answer. It was a randomised multicentre phase II trial just for hypothesis generating because we don’t want to make immediately a phase III trial because when we don’t find any reason to continue with a very large trial we first wanted to show superiority, or a hint for that, in a phase II study. In the end we randomised 122 patients, however the maintenance did not improve neither the progression free survival and also not the overall survival.
Negative results are still results, what are the plans to take these data forwards and incorporate them into future trials?
Negative results are also very important results because many people in many countries were asking if the maintenance should be added to every chemotherapy in patients when they’re treated for mantle cell lymphoma. In particular there was, some years ago, a publication in The New England Journal of Medicine and this was a randomised trial addressing also the question of rituximab maintenance. They had two different chemotherapy regimens, the one was CHOP-R the other was RFC, fludarabine cyclophosphamide. It came out, interestingly, that the maintenance added something to the efficacy after R-CHOP but did not improve the outcome of RFC. So that was a very important study which makes us understand it’s not so easy to extrapolate that maintenance is good, we need to test the hypothesis after each chemotherapy. Now we did it after bendamustine rituximab and I know many colleagues from many countries who extrapolated like this – if it’s good after R-CHOP it’s also good after BR, we would like to give it and where is the data. So that was the time at the ASCO because the ASCO committee selected that abstract for oral presentation. So I presented the results; somewhat they are disappointing but also in the end they are very relevant for most physicians worldwide so at least one can say that two years of additional treatment is not necessarily needed because the outcome for the patient was not improved.
That addresses every question that I had, is there anything you would like to add?
Yes, of course we further want to improve the results with bendamustine rituximab. It is a treatment which is quite well tolerated, even for a patient population in the age of 70 and older. So still we have found something, what is administerable to the patients, we want to improve the results. So the addition of cytarabine was just briefly commented by me that this was shown to be effective in some studies published in the literature however only as a phase II result. Then the addition of the new kinase inhibitor, ibrutinib, which is approved worldwide for the relapsed mantle cell lymphoma also is under investigation, there are some studies ongoing. In addition lenalidomide, the IMiD, what we know from multiple myeloma has been shown to be very effective in mantle cell lymphoma, also some studies ongoing that lenalidomide is added after BR in terms of a maintenance as we have done with rituximab. The last drug which has shown activity is bortezomib, the proteasome inhibitor, and also there are some studies ongoing worldwide where bortezomib added to bendamustine rituximab may hopefully add something to the efficacy.