Future Directions in CLL


William Wierda, MD, PhD: Thanks to all of you for this rich and informative discussion. Before we conclude, I’d like to get your final thoughts and ask what you’re most excited about in therapeutics for CLL [chronic lymphocytic leukemia]. We’ll start with Dr Burke to give Dr Allan a chance to catch his breath.

John Burke, MD: A couple of things strike me as particularly exciting. One is the novel BTK [Bruton tyrosine kinase] inhibitors, the noncovalent BTK inhibitors that we just heard about from Dr Allan. Those offer a lot of promise. The biggest challenge right now in the field are the patients with hard-to-treat CLL who progressed through the BTK inhibitor and venetoclax and maybe a PI3K inhibitor, those desperate patients who need help. The noncovalent BTK inhibitors offer potential for those folks.

The other big, exciting development is the use of MRD [minimal residual disease] to adjust therapy, not just in CLL but in a lot of fields. Think about lymphomas where we have treatments that work for a good majority of patients, but then there are patients whose cancers become resistant and then they relapse and do poorly. If we can identify who those patients are by using MRD assays to see who has residual disease, then we can tailor therapies earlier and try to make an impact when we know we have the potential to help more. In CLL, tailoring therapy based on MRD assays and result is an exciting way forward for the field.

William Wierda, MD, PhD: Dr Allan, what are you most excited about?

John Allan, MD: I’m excited about these combinations of therapies. We’re seeing great clinical synergy. We see the vast majority of patients—regardless of high-risk features—able to achieve MRD negativity, which we know translates to longer-term remission. I’m excited about that. I also echo Dr Burke a little in trying to get behind our thoughts of what is personalizing the treatments for our patients. But I really want to dive into the data and find cytogenetic abnormalities that may respond better to a certain approach.

We have a little evidence that that there may be something there with BTK inhibitors or 11q, and wecan start to tease out certain patient populations that might actually do better with a specific approach. It’s not going to be a discussion of only what the patient wants, which is what we do now, but rather we will tailor therapy to evidence-based practice guiding treatment, so we know this is going to be the best treatment for you. With maturation of all this data and larger numbers of patients being treated in uniform manners and similar populations, we’ll be able to start to tease that out and have meta-analyses type of studies. I’m excited to see research into those areas as well.

William Wierda, MD, PhD: Great. Dr Shadman?

Mazyar Shadman, MD, MPH: In addition to what was just mentioned about combination therapy and using an MRD-guided approach, I’m excited that no matter how different high-risk disease, there are patients who are still in need of different types of treatment and novel treatment approaches. It’s good to see that immunotherapy specifically is still active for CLL. We definitely do have patients who need treatment beyond what we discussed today.

Maybe this is more hopeful than exciting, but with more treatment options, I certainly hope that translates to affordability and availability for patients around the world. Hopefully more treatment options will create some competition that eventually patients will benefit from. We shouldn’t forget that these drugs are not necessarily available for all CLL patients in different countries. With more agents, there will be a situation where we can help other patients have access too.

William Wierda, MD, PhD: Again, thank you all. To our viewing audience, we hope you found this OncLive® Peer Exchange® discussion to be useful and informative. Thank you.

Transcript Edited for Clarity

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