ESH CLL 2022 | How to approach R/R CLL

This is a very important topic for us clinicians, how to treat patients. I think your question implies an aspect that will become very important in the future. Which first-line therapy do we want to give to a patient? And, what do we think is the best sequence? And of course, what is the wish of the patient? We have to consider different aspects.

Is it that the patient really wants to have a time-limited therapy, or is that aspect not so important for the patient? In which country is the patient living? I don’t think that all countries really can treat their patients with all the new fancy drugs in all the lines. So, is it a country where chemotherapy was applied in the first-line? How long was the response or the progression-free survival of the patient after therapy was finished? I think we really have to consider all those aspects to provide a really good second-or third-line therapy.

For today, I would say, a patient that is on ibrutinib treatment, and most of the patients which get ibrutinib in front line and then relapse, that is a candidate for venetoclax treatment. But in the future, we will have more and more patients that will be treated with venetoclax in first-line. And then the situation is, of course, a different one, and these patients may be other good candidates for ibrutinib.

But, of course, we also don’t know when there’s a patient who received venetoclax in first-line and then has a very long progression-free survival, over several years. Is that maybe a candidate for re-treatment with venetoclax again? I think these are things and questions that we have to answer in clinical trials, by testing, really, the optimal sequence.

And then we, of course, need to give answers on how to treat patients being refractory on BTK inhibitors and BCL-2 inhibitors. Maybe for the short term now, we have the non-covalent BTK inhibitors. That most probably will be efficient in that particular patient population, but we don’t know for how long because obviously these patients are relapsed, now going to very highly specific and efficient lines of therapy. These might be patients that also are at risk for relapse after maybe short treatment with a non-covalent BTK inhibitor.

Therefore, I think we still need to improve our cellular therapies, like CAR-T cells, the application of bispecific antibodies, and there is still some room in that scenario for allogeneic stem cell transplantation.