The Role of Transplant and Future of CLL


William G. Wierda, MD, PhD: As we finish up, maybe we can just touch on transplant. Matt, you have experience in that area and have done work with the checkpoint inhibitors in transplant. So, what’s the role for transplant in CLL?

Matthew S. Davids, MD, MMSc: Transplant has had a more limited role over the last few years compared to the past because we’ve had such great novel agents that have come into the clinic. But we have to remember for these patients with deletion 17p and complex cytogenetics, the median PFS is only in the range of 2 years in the relapsed/refractory setting. And we have venetoclax as an option for those patients. So, those patients, if they’re young and fit and have a good donor as they’re getting into, maybe in second-line of therapy, we do need to be starting to think about transplant in that setting for a long-term survival right now. That’s still the only modality we can have for those patients that’s going to be successful.

Nicole Lamanna, MD: I also do think that it’s certainly, in my experience, been a little bit easier now to get some of the patients to transplant who I could never get to transplant before after chemoimmunotherapy when they were multiply relapsed just because they were so beaten up or they had infectious complications. You couldn’t get them to the transplant for those who you could transplant. Now, actually having drugs like venetoclax and ibrutinib, you can sequence then and get some of those individuals to transplant who you might not have been able to in a previous era. So, it is very exciting, although albeit I agree with Matt. Certainly, far less transplants now than we used to do.

Shuo Ma, MD, PhD: And the important thing that affects the transplant outcome is whether you can have disease really well controlled prior to transplant. So, my approach is that I want to make sure before I exhaust my last best option for the patient’s treatment, you want to get them into good disease control and that’s the point of going to transplant.

Steven Coutre, MD: Hopefully, CAR T cells move into the conversation here in lieu of transplant. So, we’ll see how that goes.

William G. Wierda, MD, PhD: I think we’re going in that direction. Each of the companies who have developed CAR T-cell strategies are now interested in CLL. I’m aware of trials that are being planned for each of those. So, we will have that option. The effectiveness perhaps may have been a bit more modest in CLL compared to ALL. We’ll work through that. And then the tolerability is the other issue in CLL. When you have patients who have been on oral agents and you’re working to give them the CAR T-cell therapy, there still are challenges with the neurotoxicity.

This has been a great discussion. As we wrap up, I’d like to ask each of our panelists to provide some additional key thoughts regarding what we’ve covered throughout this program. We could start maybe with Steven.

Steven Coutre, MD: I think the takeaway for me is really starting to look at the novel-novel combinations, particularly in the upfront setting, and looking towards time-limited therapy.

William G. Wierda, MD, PhD: Nicole?

Nicole Lamanna, MD: He stole my thunder. I think we have to just acknowledge the fact that we’re in an era that really has been wonderful to be in with these new therapies. And so, as we look for time-limited duration and look at MRD negativity to lead us into whether or not we can have long progression or patients off of therapy for a very long period of time, reintroduce these agents and see if they’re still sensitive to these agents. I think it’s an exciting time to be in, albeit we still have to balance toxicity issues. So, I agree with Steve to still keep in mind that what may fit one may not fit another. And so, there are some of those patients who will do fine with just sprinkling very little therapy for their disease. And it would be nice if we could figure out who those are and then do that with them and everybody else do the other. So, a very exciting time.

William G. Wierda, MD, PhD: Shuo?

Shuo Ma, MD, PhD: Yes. So, I think it’s a very exciting time because of all the novel therapies. And now our goal is to develop new generations of therapy trying to minimize the toxicity with the oral agents, and also to improve upon what we already have, too, by doing the novel-novel combinations or novel conventional triple combinations to achieve a really deep response. MRD negativity now is definitely achievable, and hopefully that will translate into a very long progression-free survival.

Matthew S. Davids, MD, MMSc: And I certainly agree with everything that has been said. We’re well into the novel agent era, but we’re really kind of at the end of the beginning of this era. This is an era that started mainly with novel agent monotherapies and now we’ve entered this middle ground where we have some combination therapies coming along. I still don’t think we know what the optimal combination therapies are. And they may be novel-novel, but they may be novel with chemotherapy or they may be novel with a CD20 antibody. So, I think we need a lot of ongoing clinical trials and I strongly encourage local physicians and community doctors to refer in for clinical trials. We have a lot of exciting plans for trials in the future.

William G. Wierda, MD, PhD: Yes, and I would agree. There are really a lot of data that we need to keep up with. There’s a lot of education that needs to be done. There’s a lot of sorting through how best to approach patients and to manage patients. In the past, we used to talk about no improvement in overall survival in the randomized trials. Now, that’s a routine conversation where we’re seeing improvement in overall survival in patients who are getting even the new novel monotherapy strategies. So, I’m very optimistic that things will continue to rapidly progress in terms of how we can best manage our patients. Thank you. On behalf of our panel, we’d like to thank you for joining us for this OncLive® Peer Exchange®.

Transcript Edited for Clarity

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