Understanding CLL Remission

Our recent CLL Global Research Foundation Town Hall featured CLL Global President, Dr. William Wierda, and Dr. Constantine Tam from Monash University in Melbourne. CLL patient advocate Jeff Folloder moderated the event. Watch the full webinar.

Transcript

Jeff Folloder:                          

Leanne wants to know, what percentage of patients stay in remission? She’s 77. It’s a good question to ask. How many of us are going to stick in remission? Dr. Wierda, you’re up first.

Dr. William Wierda:               

That’s a complicated question. I think you have to start out with the discussion that there are two strategies that you can take for treatment. One is a maintenance strategy. And you can achieve a remission with a maintenance strategy, but it’s not deep enough to get you off treatment. But it is considered remission, and you stay on treatment. In that setting, with the data that we have currently available, the average duration that a drug like ibrutinib works as a maintenance is about nine years. And that’s pretty good. And that’s pretty good, especially since there are other options that we have available if that fails, if ibrutinib fails.

I expect that the outcomes will be even better with acalabrutinib and zanubrutinib, because they’re better tolerated. And I think in general, patients probably fare better with those drugs than they have historically with ibrutinib.

The other strategy is fixed duration or time-limited therapy, where the goal is to get patients in a good deep remission, and have a period off treatment in remission. And then if the disease comes back, we can retreat with that same strategy. If patients have a very short remission or if they don’t respond to the treatment in that setting, then we switch to a BTK inhibitor-based therapy. So, we can switch in that instance where we don’t get long enough remission or we’re not getting a remission with venetoclax-based therapy.

So, the time limited or fixed duration. The data that we have right now available is with the CLL-14 trial. That trial showed that the average duration of remission, or the median progression-free survival was overall six years. It’s a bit shorter for patients who have an unmutated immunoglobulin gene. It’s a bit shorter for patients who have 17p deletion.

But on average, the median progression-free survival is six years. That doesn’t mean patients who have progression need treatment. So, the time to next treatment is longer. And again, as I said, if patients have their disease come back, it is a reasonable option to go back to venetoclax. We don’t yet know what the average duration of remission is with our combined target therapies. Ibrutinib plus venetoclax, acalabrutinib plus venetoclax, or the triplets. I’m confident that it will be better than what we’ve seen with CLL-14.

So, it’s a tough question. And, unfortunately, or, fortunately, it takes a long follow-up to have an understanding of what the remission duration is and how long these treatments are effective. But you can, as you can tell, it’s a long time. And to the point where I think we have so many options and we have such effective therapy, that somebody who’s over 65, even if they need treatment, their lifespan’s probably not going to be shortened by their diagnosis of CLL.