CLL Treatment Options

Whether you're on watch and wait or need treatment soon, this video will help you understand a few of those treatment options, what the side effects are, and what successful treatment looks like. So the main two classes of first line therapy are group of medicines called BTK inhibitors, and another group called BCLL two inhibitors. But that second one is mostly just one medicine called venetoclax. A few different BTK inhibitors, and venetoclax. And the truth is, we really can use either of them as first line therapies. They are both targeted therapies. They're not chemo. There's a few differences between them, but they're both overall very well tolerated. And they put the great majority of patients into remission. One of the major really advances for CLL and other related B-cell malignancies have been BTK or Bruton's tyrosine kinase inhibitors. These are drugs like a ibrutinib, acalabrutinib, Zanabrutinib that are FDA approved for CLL both as first treatment and also for CLL if you haven't had this drug in the relapsed setting after other prior treatment. This class of drugs is a pill based treatment. And as a class, you know, there's a little bit of differences between the different drugs between ibrutinib, acalabrutinib, and zanabrutinib, but they do share some commonalities in the overall side effects. So one of the major things we see with really as side effects, with all CLL treatments, as these treatments do have the ability to decrease the blood counts sometimes, often before they get better. And so you might have lower hemoglobin, lower platelets, in some cases lower white blood cell count. However, actually with the BTK inhibitors these drugs often when a patient first starts the drug, we actually see the white blood cell count go up even further. That's something called a lymphocytosis or the lymphocyte count increases because interestingly, the CLL drug works by you can think you have CLL cells in lymph nodes. It's working. It's actually releasing some of the CLL cells from the lymph nodes and pushing them out into the blood compartment. So I always tell patients to expect that. But you know, right after they start the BTK inhibitors. And it's not that they're not that the treatments not working, but really an expected byproduct of starting the drug. The other major side effects that we can see are there is an increased risk of bleeding with these drugs. And so for patients who are on a blood thinner already, we have a discussion about the safety of that, whether it makes sense for the patient to do this or another treatment option. But there are patients that can safely do both. And then if patients are scheduled for procedures, patients often will need to hold the drug for a period before and after the procedure. So it's really important to talk to your doctor and let them know that that procedure is happening. The other thing that we've seen with BTK inhibitors is that they can have cardiovascular side effects, and so they can increase the blood pressure. So that's something that we very carefully monitor at our visits. And often for patients with preexisting heart issues or hypertension, high blood pressure, I'll actually have a discussion with the cardiologist or primary care physician before they actually start the drug to make sure that we have a good plan should we encounter higher blood pressure. And then the other risk we talk a lot about is a risk for a heart arrhythmia or atrial fibrillation. This is an abnormal heartbeat. It's common in the general population. But we actually do see a higher rate in patients who take ibrutinib, acalabrutinib, or zanabrutinib, there's some differences between each drug. And sometimes we select the drug based on the patient there. It does look like ibrutinib this risk is higher we know now than with acalabrutinib or zanabrutinib. For patients who have a history of AFib or other heart condition, I really usually do do a cardiac evaluation before and work with a cardiologist to make sure that we have a safe plan going into starting the treatment. Most patients actually, while there's a host of side effects that come up, I would say, you know, in general patients tolerate the side effects really well. I think it's always a good idea to talk to your doctor and the health care team, the nurses, nurse practitioners, pharmacists, if available, to kind of know what the side effects are and just have a plan to call your doctor if they come up. But I will say, actually, many patients start the drug and don't have any side effects. And some of these side effects, like the high blood pressure, can be cumulative over time. But some of the other side effects, for example, acalabrutinib many times patients will get a headache in the first few weeks of taking the drug. It responds well to Tylenol, caffeine, and then it often goes away. So just really again, staying attuned to the side effects. But you might, you know, as a patient, start the drug and not experience any side effect. And these are pill based medicines that patients are able to take once or twice a day, depending on which one is selected for you, but often tolerated very, very well. The BTK inhibitor pills also very simple, very well tolerated, maybe a bit simpler in the beginning. And the main difference is patients usually take those BTK inhibitors. These are medicines like acalabrutinib, zanabrutinib, ibrutinib. They take those for as long as they're working and not causing any side effects. Just the way you take a blood pressure medicine or a cholesterol medicine. So some patients profound prefer that kind of simplicity of the BTK inhibitors. Venetoclax is a oral medication that we use to treat CLL or SLL, and it's what we call an anti-apoptotic inhibitor. This flips cells from staying alive too long to rapid cell death or apoptosis. Which is a good thing, of course, when you're talking about wanting to kill the leukemia or lymphoma. But that rapid cell death does owe to some of the side effects in the toxicities that we monitor for while patients are on therapy. In CLL, venetoclax is used both as a first treatment in combination with other medications for CLL. And it's what we call time limited. And for patients with previously treated or relapsed or refractory disease also usually done time limited. The difference is as a first treatment, it's often done in combination with an antibody called obinutuzumab anti CD20 antibody and the venetoclax is for one year. For patients with previously treated CLL. The combination of venetoclax with an anti Cd20 is for usually two years of the venetoclax. Those are the standard approved ways that we use venetoclax. So venetoclax is an oral drug. So it's a pill. When its first started in combination with an antibody it is ramped up. So though it's a pill, the dose of it changes the first week to the second week to the third week. Sometimes the dose does change according to if patients are on other medications that might interact, or in some cases if patients run into side effects or blood count, cytopenias, then the dose has to be appropriately reduced. So the side effects with venetoclax I generally think in two ways. One, of course, are importantly what we're asking patients to report to us, what they feel or experience. And overall, venetoclax is generally pretty well tolerated. Some patients can have nausea or GI symptoms, such as loose stool or diarrhea. Some patients can have rashes or fatigue, but many patients on a day to day basis from the drug itself feel okay. The second category I think of side effects are the things we're watching out for and sometimes have become very severe, such as extreme cytopenias, patients may be more at risk of infections or bleeding. For the tumor lysis, again, patients may not feel a difference, but we're watching very closely tumor lysis, increase in potassium, phosphorus, decrease in calcium, increase in renal dysfunction for example. For the day to day side effects such as nausea or loose stool. Most of those we can give other supportive medications. Patients do okay and we guide them through them. If they become much more severe, in some cases, patients have to lower the dose of the medication. In terms of tumor lysis, a lot of it is about prevention. So before we even start the medication education with the patients about hydration, monitoring, as I mentioned, the dose ramp up. And then in terms of cytopenias, again the frequency of monitoring plays a role. For things like neutropenia which happens in about half of patients get three four neutropenia. If we’re watching for that and catch it early without fevers, we can give growth factor medications to support patients. They may not even have to interrupt drug therapy during that time. Whether you decide to go with BTK inhibitors or BCL two inhibitors, the choice is up to you and your medical team. Once you've started a therapy, what then is the goal for treatment? Success is really all three of these things. It's about getting patients into remission, which again, for most patients, we're able to do, thankfully without too much hard work. Then the other part of success is staying in remission for a long time. But really, the most important part of that success is for the patients that have good quality of life. During that time and again, if folks were working full time, most of our patients should still be working full time. If patients do have side effects, it's just about being attentive to see if we need to sometimes change the medicine, change the dose of the medicine, or actually change the medicine itself, or just do some sort of conservative management to take care of some of those side effects. So the goal is remission, long lasting remission, and good quality of life during all that time. In February of 2026, the FDA approved the combination of acalbrutinib with venetoclax to create the first all oral fixed duration frontline therapy for CLL patients. Current treatments allow CLL patients to live long, healthy lives, but they are still not curative. Doctors and researchers are always working towards a cure, and this progress is being made through clinical trials. Clinical trials and research is really why we have made so much progress in CLL treatment so far and why we have all the current available therapies for CLL. And so I think it's quite important for you to see a provider or a doctor who may present you with some standard of care options of treatment, but also clinical trial options. HealthTree offers a free, personalized clinical trial finder to find trials that you may be eligible for. To learn more, click the link in the description. No matter the treatment, the goals are the same; to control the disease, achieve remission when possible, and preserve quality of life. Now that you have a basic knowledge of CLL treatment, we encourage you to work with your medical team to decide what's best for you.