Monitoring Treatment Reponses in CLL: A Review of Key Protocols

Announcer:
You’re listening to Project Oncology on ReachMD, and this episode is sponsored by Lilly. Here’s your host, Dr. Charles Turck.

Dr. Turck:
Welcome to Project Oncology on ReachMD. I’m Dr. Charles Turck, and joining me to discuss protocols for monitoring treatment responses in patients with chronic lymphocytic leukemia, or CLL for short, is Dr. Lindsey Roeker, who’s a hematologist and medical oncologist at the Memorial Sloan Kettering Cancer Center in New York City. Dr. Roeker, thanks for being here today.

Dr. Roeker: 
Thanks so much for having me.

Dr. Turck:
So to get us started, Dr. Roeker, what are some signs that we want to be on the lookout for, that a patient with CLL isn't responding to treatment?

Dr. Roeker: 
When I'm taking a look at a patient in front of me, I'm watching their CBC and I'm watching their physical exam. So I'm making sure that I'm understanding what's happening to their hemoglobin and their platelets. If those were cytopenias that we were dealing with in the beginning, are those improving? And then I'm also looking for a reduction in lymph node size and reduction in splenomegaly. And those are really all of the features that I'm taking in aggregate to help me understand how a patient is responding.

Dr. Turck:
Well, given those signs, let's zero in on monitoring protocols. How and when should we monitor a patient's response to treatment?

Dr. Roeker: 
So when I'm using a covalent BTK inhibitor, I often do a first check of their CBC a couple of weeks into therapy, just to ensure that there aren't any significant changes in their counts or worsening of pre-existing cytopenias. And then if everything's going well, they're tolerating the drug well, and their blood counts all look good, then I go to less frequent monitoring. And monitoring in that case really focuses on a CBC, a comp, and then a physical exam to look for lymphadenopathy and splenomegaly. And those are really the tools I use to monitor therapy.

If it's a venetoclax-based approach, obviously there's a lot more monitoring right in the beginning because we need to be looking for tumor lysis syndrome. That treatment requires a 5-week dose escalation with monitoring for tumor lysis syndrome. Thereafter, it really depends on how a patient is doing, and how frequently I check in on them really depends on that piece. Often, venetoclax is given in combination with a CD20 monoclonal antibody, so I'm seeing them monthly anyway while I'm administering that antibody. But for that treatment, I'm also utilizing the same tools. So I'm looking for clinical response with blood counts and a physical exam.

Dr. Turck:
And if we notice a poor response to therapy, what should our next steps be?

Dr. Roeker: 
So this is a good question because often, these drugs have such high overall response rates that we do see responses. The true refractory patient is actually relatively rare. But if we're seeing that counts are really poor or that lymph nodes are actually growing despite therapy, I think it's always good to take a step back and ensure that you understand exactly why that treatment isn't working. So if you have a lymph node that's growing through therapy, it's often worth considering whether you need to perform a PET scan or a biopsy of a node to ensure that there is not a Richter's transformation or a development of a more aggressive lymphoma or to also look at whether we're seeing a node that's growing and has developed a resistance mutation. So I think some of those tools can be helpful in terms of monitoring.

If you have a patient who has cytopenias that are really not at all responding to therapy, that's when a bone marrow biopsy can be really helpful in making sure that you understand is this just refractory CLL, so the bone marrow is actually packed full of CLL cells? Or is this development of a new problem that's driving the cytopenias? Because those should be managed differently depending on what we see.

Dr. Turck:
For those just tuning in, you're listening to Project Oncology on ReachMD. I'm Dr. Charles Turck, and I'm speaking with Dr. Lindsey Roeker about how we can monitor patient response to treatment for chronic lymphocytic leukemia.

So, Dr. Roeker, now that we know what these monitoring protocols look like, let's turn our attention to how we can better integrate them into practice. What are some challenges clinicians often encounter when applying these protocols or monitoring patients, and do you have any recommendations on how we can overcome those challenges?

Dr. Roeker: 
So I think relative to some diseases where, you know, you have frequent need for scans and follow-up, in some ways, these are easier. But in some ways, patients also say, “I'm just on a medication, and everything's going fine.” So there can be some laxity in that piece. So I talk to patients a lot about how important it is that they do come to clinic and have periodic check-ins to make sure that the drug is working the way we expect it to be working, to make sure their blood counts are okay, and to make sure their kidney and liver function is looking okay. I think as long as patients understand why that's really the focus and that that's the part that is really important, people are more able to comply with protocols when they understand why they're being done. So I do try to make sure that my patients are well educated on those pieces.

Dr. Turck:
And before we close Dr. Roeker, are there any key takeaways you'd like to share with our audience on monitoring responses to CLL treatment?

Dr. Roeker: 
While you're monitoring response, it's always tricky to know exactly what you're dealing with. If a progression event is happening and it's not really obvious, I think it's always good to take a step back and use time on your side. So watch things over time. And it's always okay to watch more closely. But sometimes you can see kind of transient increases in a white count or transient dips in counts due to nutritional deficiencies or illnesses or things like that. And it's always good to watch over time to ensure that you really understand if this is truly a progression or not. Because we have really effective therapies for CLL, but we also want to make sure that we are getting as much mileage out of each line of therapy as possible. So if you are concerned that there's progression, I think checking in in short order with the patient in terms of was that a transient change? Or is it a trend that we're really seeing constitutes progression? Because at that point, that's when a change in therapy is needed. But sometimes, we can see these little changes that we might be able to, with more follow-up, recognize were actually not progression events. So I think that's one thing that can be very valuable for these patients.

Dr. Turck:
Well, with those final thoughts in mind, I want to thank my guest, Dr. Lindsey Roeker, for joining me to discuss monitoring protocols for patients with chronic lymphocytic leukemia. Dr. Roeker, it was great having you on the program.

Dr. Roeker: 
Thanks so much for having me.

Announcer:
This episode of Project Oncology was sponsored by Lilly. To access this and other episodes in our series, visit Project Oncology on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!