How are treatment plans developed for patients with CLL?

We’re actually quite lucky that these two targeted therapy classes, the BTK inhibitors and the BCL2 inhibitors, are both so good and mostly well tolerated that I would say, speaking for myself and a lot of other CLL doctors, we're a bit open minded as to which way to start. You know, they're both good roads. Here in New York, we say you could take the Long Island Expressway or the Grand Central and you'll still get to Huntington at around the same amount of time. And therefore, with BTK inhibitors and with BCL2 inhibitors, since most patients are doing well because there are a few little differences in sort of the practical aspects of it, patients are involved in that decision. One example of the things that patients have feelings about is venetoclax. That BCL2 inhibitor is usually used in a time-limited way, just for one year for most patients, and then they get a break from therapy. And some patients like that a lot. But that therapy’s a little bit more complicated in the beginning with some intravenous parts of it. The venetoclax is a pill, but we usually combine it with an intravenous immunotherapy. So that’s a bit more complicated in the beginning. The BTK inhibitor pills are also very simple, very well tolerated, maybe a bit simpler in the beginning. And the main differences: patients usually take those BTK inhibitors—these are medicines like acalabrutinib, zanubrutinib, 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 prefer that kind of simplicity of the BTK inhibitors. Some patients prefer the time-limited, “I get to take a break after a year” most of the time then. So patients should be involved in that decision.

So fundamental, the first thing is meeting the patient themselves, trying to figure out what the CLL looks like, how aggressive it is, what’s the molecular profile of CLL and how they are going to anticipate that the CLL would progress over the next several years and what effect that would have on the patient’s life itself, whether it’s going to affect the patient tremendously in their normal day-to-day work and their life’s goals, or if it would just be a part of the patient and not really affect. Once those kind of determinations have been done, they also try to see how fit the patient is and what kind of treatment plan would lead to the best quality of life, least toxic therapies, and that a patient can tolerate. And that would be the way they would profile a patient and choose a suitable combination drug.

What should a CLL patient consider and be prepared for when deciding on a treatment plan?

The first thing to realize is that CLL is a little different kind of cancer and just having a diagnosis does not really clearly tell out the path that the CLL might have. I know the word cancer or diagnosis of a blood cancer itself is very anxiety-provoking. But sometimes it is important to understand that not all cancers are equal and not everything is going to be addressed the same way. Some cancers are much slower growing. Some of them can be watched and try to assess that portion and to take that seriously. And then the next thing to understand would be to figure out how fit they are. Sometimes patients can overestimate how well they would respond to the toxicities of the therapies. And it’s important to realize that many of these therapies that we offer to our patients, unfortunately, have toxicities, and one has to carefully balance the benefits versus the risk. And third, gather as much information as possible, but take it to the oncologist and have faith in the oncologist to be able to take into account all this information that is available out there to come up with the best plan. And I keep emphasizing the partnership with oncologists to come up with the right kind of plan.

How will the doctor determine which treatment option is best for the patient?

For these first-line therapies, BTK inhibitors and BCL2 inhibitors, there are these little differences. One difference I mentioned is that venetoclax is usually used in the beginning with intravenous immune therapy. One example of that is something called obinutuzumab. So it’s an antibody, it’s not chemotherapy, it’s intravenous. And some patients just don’t like the sound of any intravenous therapy at all. They think that IV therapy sounds scary. It’s very reasonable, even though this is a fairly simple IV therapy, for some patients they may not even have good veins, even though these are gentle therapies and they’re pretty gentle on the veins. If some patients just feel they do not want any IV therapy at all, then we would probably give them BTK inhibitors. They’re quite simple and don’t usually involve any IV therapy. If patients had a very high, we say tumor burden, their CLL counts were extremely high, then it might be a little bit easier and gentler to start them on the BTK inhibitor, because the risk of some of the side effects in the beginning with venetoclax might be a bit more. But for most patients, they probably could tolerate and have a great response with either of these first-line approaches. So for most patients, their feelings about it are an important part of that decision.