Understanding What the CLL 10-Year Progression-Free Survival of Ibrutinib Means

Our recent CLL Global Research Foundation virtual town hall featured CLL Global President, Dr. William Wierda, and Dr. Patrick Reville, Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. CLL patient advocate Jeff Folloder moderated the event. Watch the full webinar.

Transcript

Jeff Folloder:

Dr. Wierda, a question came in just a few moments ago. It’s in regard to the 10-year average that you were talking about earlier in the presentation. They say, “I saw where you had the 10-year average of effectiveness for ibrutinib (Imbruvica). Do you mean by this that that is the average number of years that you have seen ibrutinib continue to be effective?” Question.

 “Or” – well, the reason is – the reason why he’s asking is that he’s been on ibrutinib for nine years now and wants to know what comes next.

Dr. William Wierda:

Yes. So, it’s a little bit complicated to explain. So, it’s a median progression-free survival of 10 years. So, progression-free survival means no – and there are specific criteria we use for progression, no progression, and the median means if you take 100 patients and put 100 patients on ibrutinib, patient number 50 will have progression of their disease at 10 years.

So, you’ll have patient 1 through 50 potentially progressing before 10-year time point, and then you’ll have the other half of the patients, patient number 51 to 100, who are still having good disease control on ibrutinib at that 10-year time point.

So, it’s the median. It tells us the time that – it’s not the average. It’s sort of where that middle patient, how long that middle patient has disease control or progression-free survival. So, the answer to the question is it’s easier – because I think people understand – lay people understand it a little bit better by just saying the average length of time that the drug works is 10 years.

That means that on average, half the patients will have a shorter response duration, half of them will have a longer response duration.

And the other thing to keep in mind is that with ibrutinib, we see a fair number of patients coming off of ibrutinib for some side effect or toxicity. That doesn’t mean that a BTK inhibitor won’t continue to work for those patients.

So, now we have a situation where, okay, if a patient is on ibrutinib for five years or four years and they have to come off ibrutinib because they have some muscle pains or joint aches and pains, they can switch over to acalabrutinib or zanubrutinib in that situation and expect to have a long period of response to treatment, at least that 10 years or longer.

And that’s a little bit different than the way those data were generated because if a patient comes off ibrutinib for intolerance in that trial, they’re monitored for progression on observation, not additional treatment, and so that 10-year time point also includes patients who have stopped early because of intolerance. And their disease progressed, and then they to on to a subsequent therapy.

Hopefully that’s – it’s a complicated concept, or several complicated concepts, but I think the important point is that you can expect, on average, a response duration of 10 years or more with the BTK inhibitors.

It may be better for the second generation BTK inhibitors, acala and zanu.