SOHO 2026 | Practical barriers to community adoption of fixed-duration regimens in CLL

So in the field of CLL, continuous therapy is one paradigm which was established very originally when ibrutinib was approved for CLL back in February of 2014, so about slightly more than a decade ago. And that established a paradigm of continuous BTK therapy, and then subsequently we had zanubrutinib, we have acalabrutinib approved in the same setting, continuous BTK therapy. In terms of the time-limited approaches, up until recently, the only time-limited approach in frontline CLL was venetoclax plus obinutuzumab given for a duration of one year. And that also has been approved for now last, I think, seven, eight years. The issue with venetoclax plus obinutuzumab, especially in the adoption in the community setting, has been the monitoring for tumor lysis syndrome for venetoclax and also the infusions with obinutuzumab, which are given kind of weekly in the first month and then once a month. So practically, if you follow the guidelines of the CLL-14 trial or the regimens, patients will be coming to the clinic almost every week for the first two months of the regimen. And many times they have to come two consecutive days when they’re doing the venetoclax dose-escalation. And so that kind of creates a problem in terms of practices where they’re not attuned to checking TLS labs, especially TLS labs in the afternoon, and then they have to check the next day morning. It also adds a bit more complexity, obviously, logistically for the patients to come back and forth to the clinic. So I think that, in my opinion, has been the biggest barrier in terms of adoption of time-limited approach in the U.S. Now, having said that, more recently, we have an approval of a second time-limited therapy approval in the U.S., namely acalabrutinib plus venetoclax, based on the AMPLIFY study, I know ex-U.S., we already had ibrutinib plus venetoclax approved but this has not been approved in the U.S. So for the US perspective, now that we have acalabrutinib plus venetoclax approved, that makes things a bit more simpler because we are not talking about IV infusions. We’re only talking about two pills. So logistically, it makes things much easier. I think one of the things we are waiting for is long-term data of the AMPLIFY study to see if this doublet of acalabrutinib plus venetoclax will lead to long-lasting remissions because we know that the MRD rates were not as high numerically as we would maybe wanted to see or as we have seen with ven plus obinutuzumab. So I think, you know, we are going to see more frontline approaches coming along. For example, there are trials looking at zanubrutinib with sonrotoclax in the first-line CLL, including randomized Phase III studies. So when these studies read out, I think we’ll have a better understanding and maybe, you know, more active doublet therapies approved for patients with CLL, which will make, I think, the adoption of time-limited approaches much more widely in the U.S. community setting.

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