ICML 2021 | Geltamo IMCL-2015: ibrutinib and rituximab in MCL

Good morning. The idea of the IMCL 2015 study was to try to investigate a new approach to the treatment of mantle cell lymphoma patients. And we decide to try the Ibrutinib in combination with rituximab for treating those patients placed in the most favorable spectrum of mantle cell lymphoma, that are those patients with in general would risk clinical features that nowadays we can also consider to leave them in observation. It’s true that nowadays, we still lack any consensus criteria on which are the criteria we need to apply to consider a patient candidate to observation, or even which criteria we’ll use to decide when to initiate treatment.

So this has been always a matter of a lot of discussion. And in fact, there were several groups that in the past applied to try the observation. And now it seems more accepted that we can do that. Of course, always under the close observation of our patients. And we know that this observation really is a safe procedure, but of course, we need to monitor closely the patients. And sometimes the patients develop progression, so we need to treat them.

Then another aspect that is relevant is maybe that we could tailor a little bit the treatment for those patients, as usually they behave more favorably than others. And for the reason with the eruption of this new drugs was probably a best moment to try to do so. And well, we were able to design this trial in 2014. And now, we could start it running and recruiting patients in 2016. It ended the recruitment at the end of 2019.

And we already have the results in these first 50 patients included in the trial. We have the response rate and the MLB data done at one year of treatment. That was the time point that was set as the primary efficacy endpoint of the study, the overall response rate and the CRA of these patients at that moment. So the results I think are excellent in the sense that after 33 months, we haven’t seen many progressions, only four patients progressed.

And importantly, what we can advance is that we realize that three out of this four progressions occured in patients having the TP53 mutations in addition to a complex karyotype. So again, this usually well-known poor risk biological prognostic factors seems also to affect a lot the result of these new combinations. But focused on all the other patients, the results are excellent. And this combination looks like that can be given with an barely acceptable toxicity. And the results are outstanding in the sense that the overall response rates are really high or are 80%, even over 80% of complete remissions that seems also to improve a long time.

So at the end, this is an excellent combination. And what maybe is the most new point of the study is that we have started demonstrating that this can be also given in a limited duration, not as an indefinite treatment but just with a duration of the treatment limited to two years. Of course, these, we have done it driven by MRD. So we realize, or we started seeing that the majority of patients that can effectively start the treatment after two years. And it looks like for the moment that many of them continue to be MRD negative for a long time.