Dr. Matthew Davids discusses factors that can impact a chronic lymphocytic leukemia (CLL) patient’s treatment course, including genetic testing results, age and co-existing conditions.
Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.
Dr. Matthew Davids
So, there are a number of different factors that go into the decision of which of these regimens to choose for the initial therapy of CLL. One of them is certainly the age and fitness level of the patient and what other medical issues they have. So, as patients get above the age 65, they typically may have other medical issues and may not tolerate more aggressive chemoimmunotherapy-based regimens like FCR. But they could certainly tolerate the novel agent regimens like ibrutinib or venetoclax plus obinutuzumab.
Another consideration that comes into play is the biology of the CLL cells themselves. Some patients with CLL have a higher risk form of the disease. We call this either deletion 17p or TP53 mutation. And those patients typically do not benefit as much from chemoimmunotherapy.
So, even younger patients there, we think about a novel agent-based approach. And we have, again, the longest-term data on ibrutinib for that population, although venetoclax plus obinutuzumab is also a consideration.
And then as we think about debating between these different options, we also think about the specific other medical issues that a patient may have. So, ibrutinib does have some risks in terms of atrial fibrillation, which is an abnormal heart rhythm. It can cause patients to be a bit more prone to bleeding or bruising. And so, for patients who have these existing risks, if they have heart disease already, or if they’ve had issues with bleeding recently, ibrutinib may not be the best option, and venetoclax plus obinutuzumab would be appealing for a patient like that.
Now, with venetoclax and obinutuzumab, it can be such a potent regimen that it can break the tumor cells open too quickly. This is something we call tumor lysis syndrome. It’s not something we’ve seen commonly with this regimen. But we do watch patients very closely when they’re first dosing.And so, for example, patients who have poor kidney function might be at a higher risk for this side effect. And those might be patients, again, where we think about ibrutinib as a very good option, since it’s very well tolerated even by patients who have issues with their kidneys.
So, those are some of the factors that go into it. Certainly, patient preference makes a big difference. Some patients don’t mind the idea of going on a pill, and they like the idea that it’ll control their disease in the long term. And so there, a therapy like ibrutinib may make a lot of sense. Other patients may find that they prefer what we call a time-limited strategy. And using the venetoclax plus obinutuzumab makes a lot of sense there because it’s a one-year regimen, and they can stop. But we don’t know yet the durability of those effects. So, those are some of the factors that go into making this important decision as to what to receive for a first therapy.
I think patients have an increasingly large role in making treatment decisions about what they would like to receive, especially for their first therapy for CLL. It used to be that we had very limited treatment options for CLL, and really the only choice was chemotherapy. And so, that was a pretty easy choice if you had no other options.
So now, as I’ve highlighted, we have multiple different choices. We have chemotherapy-based approaches. We have novel agent approaches, both continuous and time limited. And so, I think it’s helpful for patients to educate themselves about the pros and cons of these different options, to get input from a CLL specialist, if possible, and certainly from their oncologist as well as family members and friends, particularly if they have had friends who’ve gone through this. Getting their advice can be helpful.
And reaching out to online supports as well can be a useful thing in terms of educating oneself. And at the end of the day, the patient has to make the decision as to what they think is best for them.
And it might be a different decision for each individual patient. But the good news for patients, even though it can be challenging to make this decision, all of these options are good ones. And so, there isn’t really a wrong decision here. But there may be some that are better suited for individual patients based on their own preferences.