Selection of BTK inhibitors for the treatment of CLL

Javier Pinilla-Ibarz, MD, PhD: In terms of selecting a BTK [Bruton tyrosine kinase] CLL inhibitor [chronic lymphocytic leukemia] therapy, Katie, what are your thoughts on cytogenetic abnormalities, patients, and other factors that may weigh in as we begin to select BTK inhibitors?

Katie Tobon, PharmD, BCOP: That’s an excellent question. Shared decision making is our approach to BTK inhibitor therapy at our facility [Moffitt Cancer Center]. Data showed prolonged progression-free survival, especially with the ability to overcome adverse prognostic factors, such as IGHV. This would generally give us a shorter progression-free survival. All cytogenetic abnormalities are eligible, but it is important to keep in mind that our 17p or TP53 patients have the shortest progression-free survival. For patient-related factors, there are a lot of things we need to think about. We must take into account the age of the patient and the comorbid conditions that he may have, in particular a cardiac history. Cardiac history is an important thing to keep in mind when talking about BTK inhibitors, as well as first and second generation. This includes arrhythmias, hypertension, history of bleeding, and any other concomitant medications these patients are taking. There are many drug interactions which we will talk about soon. We must also take into account the fragility of the patient as well as the overall cost. Generally, if we have an older patient or a patient with multiple comorbid conditions that may be exacerbated, we would prefer second generation BTK inhibitors. As for treatment-related factors, this is a shared decision-making approach at our institution. Dr. Pinilla-Ibarz, what other treatment factors do you consider in these discussions with your patients in addition to what I have discussed?

Javier Pinilla-Ibarz, MD, PhD: You touched on some very important points. I want to insist on the question of cytogenetic or genomic factors. All of these generic factors predict the time it takes to reach the first treatment. When the therapy comes, obviously BTK is one of the important aspects and therapeutic strategies that we discuss with our patient. It depends on the comorbidities. We can rely more on a second or third generation BTK inhibitor. At the same time, it is important to consider patient preferences in terms if they wish to undergo fixed-term therapy in combination with BTK, can they travel to an academic institution despite the distance? In our state people are old and may not be able to drive.

I want to point out that the problem with 17p. Obviously, with 17p or TP53 transfer in the first line, we advise against [chemoimmunotherapy]. My opinions will be almost contraindicated to use chemoimmunotherapy. Of course, BTKs are a very important aspect of how we dramatically improve outcomes for patients with these genomic abnormalities. At the same time, there is no doubt that the fixed duration can be used. But we already have data showing that as soon as we stop treatment, these patients tend to relapse quickly. It is unclear how they can be retired.

In general, it is preferred to reuse BTK inhibitors until disease progression. In fact, we have some good data coming, and we’ll discuss that later. For example, in the Alliance for Clinical Trials in Oncology trial that was updated, we saw that after almost 4 years of follow-up, 17p is similar to non-17p. This trial is really encouraging and reinforces the idea that BTK inhibitors are an excellent choice for patients with these “high risk” cytogenetic abnormalities. In the past, with chemoimmunotherapy, with newer targeted therapies, maybe it wasn’t as high. It’s completely different in the second and third lines. The results for patients with targeted therapy may not be as good because we don’t have those kinds of therapies, but that’s an important factor to consider.

Transcript edited for clarity

Martin E. Berry