What Options Are Available for CLL Patients Who Relapse After Ibrutinib?

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Andrew Schorr:

Here's a question we got in from Julia and Betty and Shelly and Mark.  They all asked a similar question.  They've been on ibrutinib (Imbruvica) for five years now with success.

Is it working for most people, and what are some reasons why it doesn't work for everyone?  And then what treatment options do you recommend if they relapse on Imbruvica?  

Dr. Furman:

So right now I think the most important, there are a lot of prognostic markers available for CLL.  At last count we're probably up to 115. What's most important is in 2018 what are those prognostic markers that really are relevant to the patient, and really as long as you stay as CLL you're going to be able to have your disease very nicely controlled with our current agents and our novel agents.  

So there are certain things that do indicate patients are likely to progress on ibrutinib, not likely progress must but who may progress, and people who might need something more, and that's where a lot of our current clinical are research is focused.  So patients who have a risk of developing a Richter's transformation or patients who have a likelihood of developing a BTK mutation that might generate resistance to ibrutinib are the two groups of people that we worry about most.  

17p deletion is probably the most important predictor for predicting those patient outcomes.  There are other things that are predictive as well like having a NOTCH mutation.  Those are all readily obtainable prognostic markers that allow us to determine who's at risk and who's not at risk for progressing on ibrutinib.  If you don't have 17p deletion or NOTCH1 mutation you have almost a 99 percent chance of being free from progression at five years on ibrutinib.  And it looks like most of the people who are going to progress will progress within five years.  So I think making it to that five?year mark is really very—is the most important thing. 

Andrew Schorr:

Okay.  So if you do progress, what then?  

Dr. Furman:

So fortunately we have a lot of great agents.  

Venetoclax (Venclexta) works very effectively in patients who progress on ibrutinib, generates some very, very deep responses and very long-lasting responses.  So that's certainly one option.  Another option is to be treated with a PI3-kinase inhibitor.  So we have idelalisib (Zydelig) and duvelisib (Copiktra) now approved.  We will shortly have umbralisib approved as well as a novel agent.  We also have a whole array of other agents coming down the pipeline looking specifically at means for progression on venetoclax.  So we have an MCL1 inhibitor which targets the protein that's likely responsible for resistance to venetoclax.  So all these things are actually currently in clinical trials and certainly will hold a great deal of promise.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.