Practice-Changing Potential in CLL

Journal of Clinical Pathways spoke with Jeff Sharman, MD, Anthony Mato, MD, MSCE, and Chaitra Ujjani, MD, at the ASH Annual Meeting and Exposition about clinical trials and research in CLL that have the most potential to change the standard of care. 

Transcript

Mr Bessette: So, let me ask this, Dr Sharman. So, clearly, you are very excited about the CLL-14 trial data coming out. Are there other, are there other trials or studies that should be on the radar as individuals like yourself in this population or what are the other trials that we are most anticipating may be practice-changing?      

Dr Sharman: I think the most important one that is flying a little under the radar is ibrutinib versus acalabrutinib. We have not talked much about acalabrutinib, but it is a second BTK inhibitor that is approved and I think amongst many clinical investigators who have worked with the two drugs, I think that acalabrutinib tends to be an easier drug to administer. But we do not yet know if the efficacy is the same. There is a randomized head to head comparison study and it will be very curious to see. That could either swing things dramatically or end up being kind of a, well, choose-whichever-one-you-want type study and I do not know what that is going to show, of course.

Dr Mato, how about you? What is interesting for you?

Dr Mato: I totally agree with you about that trial in the relapse/refractory setting. One of the difficult things about trial design is that your control arm often could become irrelevant in real time. And so, at this meeting we saw the, or we will see the results of the ILLUMINATE trial comparing ibrutinib/obinutuzumab versus obinutuzumab/chlorambucil. So, that is a positive trial and you can, we could discuss those data.

But there are many other similar trials in the pipeline that also have the same control arm. And so, it will be interesting to see when we start seeing ibrutinib/obinutuzumab, acalabrutinib/obinutuzumab, venetoclax/obinutuzumab, umbralisib/obinutuzumab all potentially perform better than obinutuzumab/chlorambucil. We will be sort of left in this vacuum where we have all of these obinutuzumab plus novel agent-containing regimen, none of whom are compared directly to one another and yet, we will be forced to choose based on extrapolation.

So, I am interested to see how that pans out because I think at the end, it will not be like there is this clear-cut winner. It will be these winners who then we have to sort of think long and hard how to pick and choose appropriately. So, I am interested to see what will happen there.

Dr Ujjani: I am excited to see the results of the late-breaking abstract session tomorrow and really get a better look at the data, the SER vs the ibrutinib or rituximab regimen and really understand which of those arms are better for which sub-patient populations. But I think the specific study I am also interested in is the acalabrutinib vs ibrutinib in the relapse CLL study. Acalabrutinib does seem to be a little bit easier for patients in terms of tolerability, but I do have some concerns about the twice-a-day dosing and compliance and I think that is an important thing that we think about as we go forward as well.