Looking to the Future in CLL Treatments

Susan M. O’Brien, MD: I think targeted therapies will move earlier in treatment. We already know that for ibrutinib, where it now has a frontline indication. And there are trials, at least with venetoclax in the frontline setting, that would potentially give venetoclax a frontline approval. So, it’s very clear that venetoclax may also be a frontline choice. Idelalisib will not be a frontline choice since recently the frontline trials with idelalisib were stopped because of a higher incidence of infection and deaths in those trials. So, that drug is not going to get a frontline indication.

But, don’t forget there are next-generation novel agents also coming on to the market that are in clinical trials now. Some drugs, the ones that have been there longer, will probably have a frontline approval and some won’t, but we’ll definitely have more options for frontline treatment. Again, I think what will be very important moving forward is the ability to stop therapy, whether that comes from combinations or from patients having improved response over time. And then, at a certain period of time, one will be able to stop. I think that’s going to be very important going forward and something that I expect will change the current way we use the novel agents, which is just to give them indefinitely.

So, for the future of the novel agents in CLL, I think they are going to edge out chemoimmunotherapy. I don’t think chemoimmunotherapy is gone yet. Because of the long-term data, with CR suggesting a plateau on the curve in the mutated patients, we can’t just throw it out. We know that so far ibrutinib does not have very high CR rates in the frontline setting. My own bias is that probably the CR rates are going to continue to go up over time, the advantage of that being you’d be more likely to be willing to stop a patient who’s in complete remission, perhaps, rather than a patient who’s in partial remission. Plus, the newer agents are coming, so I think there’s no question in the next 5 to 10 years that chemotherapy will probably go by the wayside. And then, it will be a question of which novel agents produce the best responses and which ones perhaps give you such a good response—let’s say, MRD negativity—that you’ll actually be able to stop therapy.