ASH 2021 | MRD outcomes from GLOW: venetoclax and ibrutinib in CLL

The GLOW study is a study where venetoclax and ibrutinib were combined, so that is different, and the antibodies are completely oral regimen of fixed duration again, one year of treatment with venetoclax and ibrutinib. I presented the primary analysis at EHA a few months ago. And what we focus in this ASH is MRD levels. And what we actually see is indeed, that there are more patients getting to an undetectable MRD state. But we also see, maybe that’s even more relevant, is that with this combination, we get patients in deeper responses. Also, if you look to the other compartments, not only blood and marrow, but also of lymph nodes. And what we have seen, we have data on after treatment plus three months, and after treatment plus 12 months. And what you see is that patients with undetectable MRD remained extremely stable, but also patients with a positive MRD.

And that’s maybe a big difference than venetoclax and an antibody, because there you see that most patients with a MRD positive disease, or maybe borderline, they rapidly increase their cell numbers again, and disease re-emerges. And it seems very early that with venetoclax ibrutinib, although you might have MRD positive disease after treatment, it seems to be much better sustained than with the other regimens. Of course we don’t get to make that comparison, that is an ongoing CLL-17 study from a German group, also in an inter-group study. But what we actually think we see indeed, is that the VI regimen gives very good clearance of all three compartments. And if I make then a small loop to another trial that we did, is the HOVON-141, which is also discussed tomorrow morning by Carsten Niemann, the first author, the HOVON trial that we get together with the Nordic group.

And there we actually took the next step, and that’s not only giving fixed duration, but actually can you completely stop treatments when you are MRD negative? And can you restart treatment when patients become MRD positive? And the reason we did this, is if you look to a disease like CML, that’s actually what we do in that disease. And that disease, you treat until MRD negativity, and at that point you stop. And some patients will never need re-treatment, some patients will. Most of those patients, virtually 100%, will again respond to the same treatment that have been given before.

What we show in this trial is more than 200 patients, that indeed patients that … We have three cohorts. So we first gave a 15 cycle of venetoclax and ibrutinib treatment. Patients that had a MRD negative result at cycle 12 cycle and cycle 15, they were randomized to either continue ibrutinib or to stop, in a one to two ratio. Patients that stopped, a good portion of them could remain without therapy for the follow up months. But some patients also did have MRD positive disease. We re-treated those patients with the same regimen, ibrutinib, venetoclax, and virtually all patients again responded. So this might be the next step from fixed duration treatments, to MRD guided treatment, which I think is the next step in personalized medicine, what we should aim for.