EHA 2022 | Fixed-duration vs continuous therapy in CLL
Arnon Kater, MD, PhD, University of Amsterdam, Amsterdam, Netherlands, compares defined duration versus continuous therapy in chronic lymphocytic leukemia (CLL), commenting on the possibility of finding biomarkers to define the length and intensity of treatment for each patient, and highlighting promising results from the HOVON-141/VISION trial (NCT03226301). This interview took place at the European Hematology Association (EHA) Congress 2022 held in Vienna, Austria.
Transcript (edited for clarity)
We are kind of in the middle, I think, of a transition where we first showed that a fixed duration of targeted agents is beneficial and you can stop treatments. When we started the targeted agents with of course the hallmark drug being ibrutinib, can and is given continuously with very good responses for a very long time. But of course, with longer exposure to side effects, to toxicities with induction of resistant mechanism because of prolonged treatment and also, and maybe more relevant in Europe than in the US, but also financial toxicity because of the high price of these drugs...
We are kind of in the middle, I think, of a transition where we first showed that a fixed duration of targeted agents is beneficial and you can stop treatments. When we started the targeted agents with of course the hallmark drug being ibrutinib, can and is given continuously with very good responses for a very long time. But of course, with longer exposure to side effects, to toxicities with induction of resistant mechanism because of prolonged treatment and also, and maybe more relevant in Europe than in the US, but also financial toxicity because of the high price of these drugs. So then we had the fixed duration treatments, which many trials now, so venetoclax, rituximab, the MURANO study, as we just discussed was one of the first, but now we have VI, we have VO at first line, we have the triple combination all as a fixed duration treatments and it all seems to work and they all have their pros and their cons. But the next step is, instead of you treat everybody for the same duration, can you actually use biological markers to define how long you should treat patients?
And if you compare that to what is currently being done, for instance, in Hodgkin’s lymphoma, it’s also there. It’s very early markers of response in Hodgkin lymphoma. It’s a PET CT, which actually helps you in dictating how long and how intense you should treat the patients. And the idea for CLL now is after continuous treatment with targeted agents and now after fixed duration treatments, we’re actually going to have much more biologically defined treatment durations or intensifications. And we think that for sure, MRD plays a role there, maybe also level of responses, [inaudible] response play a role but the current trials that we do are very much focused on that.
And we very recently published in Lancet Oncology, the study of the NORDIC and the HOVON group, the HOVON 141/VISION trial, where we indeed could show that if we stopped ibrutinib and venetoclax combination in relapsed patients, when patients have an undetectable MRD, that was as safe as patients that continued ibrutinib monotherapy as you would normally do. And if patients had a regrowth of their tumor defined by MRD positivity, all of those patients re-responded to treatment with venetoclax and ibrutinib. And I think that’s not really already where we should be, but that’s a first step showing that indeed you can more individualized, give treatment, not on a fixed duration but on a time limited platform.
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